{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:22:34Z","timestamp":1790277754525,"version":"4.1.0"},"reference-count":239,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1450 \u2013 431460824"],"award-info":[{"award-number":["CRC 1450 \u2013 431460824"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neutrophils act as the first line of defense during infection and inflammation. Once activated, they are able to fulfil numerous tasks to fight inflammatory insults while keeping a balanced immune response. Besides well-known functions, such as phagocytosis and degranulation, neutrophils are also able to release \u201cneutrophil extracellular traps\u201d (NETs). In response to most stimuli, the neutrophils release decondensed chromatin in a NADPH oxidase-dependent manner decorated with histones and granule proteins, such as neutrophil elastase, myeloperoxidase, and cathelicidins. Although primarily supposed to prevent microbial dissemination and fight infections, there is increasing evidence that an overwhelming NET response correlates with poor outcome in many diseases. Lung-related diseases especially, such as bacterial pneumonia, cystic fibrosis, chronic obstructive pulmonary disease, aspergillosis, influenza, and COVID-19, are often affected by massive NET formation. Highly vascularized areas as in the lung are susceptible to immunothrombotic events promoted by chromatin fibers. Keeping this fragile equilibrium seems to be the key for an appropriate immune response. Therapies targeting dysregulated NET formation might positively influence many disease progressions. This review highlights recent findings on the pathophysiological influence of NET formation in different bacterial, viral, and non-infectious lung diseases and summarizes medical treatment strategies.<\/jats:p>","DOI":"10.3390\/cells10081932","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T10:47:46Z","timestamp":1627555666000},"page":"1932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A Fragile Balance: Does Neutrophil Extracellular Trap Formation Drive Pulmonary Disease Progression?"],"prefix":"10.3390","volume":"10","author":[{"given":"Helena","family":"Block","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muester, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Zarbock","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muester, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/j.1462-5822.2005.00659.x","article-title":"Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms","volume":"8","author":"Urban","year":"2006","journal-title":"Cell. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1159\/000363242","article-title":"Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extracellular trap release is regulated by macrophage migration-inhibitory factor","volume":"6","author":"Dwyer","year":"2014","journal-title":"J. Innate Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"178ra140","DOI":"10.1126\/scitranslmed.3005580","article-title":"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis","volume":"5","author":"Khandpur","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1073\/pnas.1414055112","article-title":"SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx","volume":"112","author":"Douda","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nchembio.496","article-title":"Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation","volume":"7","author":"Hakkim","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1083\/jcb.201611168","article-title":"ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation","volume":"216","author":"Stojkov","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1038\/s41467-018-05387-y","article-title":"Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production","volume":"9","author":"Amini","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/nm.4027","article-title":"Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease","volume":"22","author":"Lood","year":"2016","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.celrep.2014.06.044","article-title":"A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis","volume":"8","author":"Metzler","year":"2014","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.201006052","article-title":"Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps","volume":"191","author":"Papayannopoulos","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20100239","article-title":"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps","volume":"207","author":"Li","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3389\/fcimb.2018.00184","article-title":"Entamoeba histolytica Trophozoites Induce a Rapid Non-classical NETosis Mechanism Independent of NOX2-Derived Reactive Oxygen Species and PAD4 Activity","volume":"8","author":"Fonseca","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/jth.13239","article-title":"Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis","volume":"14","author":"Martinod","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.4049\/jimmunol.1501650","article-title":"Signal Inhibitory Receptor on Leukocytes-1 Limits the Formation of Neutrophil Extracellular Traps, but Preserves Intracellular Bacterial Killing","volume":"196","author":"Naccache","year":"2016","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.devcel.2017.10.013","article-title":"Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps","volume":"43","author":"Amulic","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, K.W., Monteleone, M., Boucher, D., Sollberger, G., Ramnath, D., Condon, N.D., von Pein, J.B., Broz, P., Sweet, M.J., and Schroder, K. (2018). Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps. Sci. Immunol., 3.","DOI":"10.1126\/sciimmunol.aar6676"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sollberger, G., Choidas, A., Burn, G.L., Habenberger, P., Di Lucrezia, R., Kordes, S., Menninger, S., Eickhoff, J., Nussbaumer, P., and Klebl, B. (2018). Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci. Immunol., 3.","DOI":"10.1126\/sciimmunol.aar6689"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nm1565","article-title":"Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood","volume":"13","author":"Clark","year":"2007","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.chom.2012.06.011","article-title":"Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis","volume":"12","author":"McDonald","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7413","DOI":"10.4049\/jimmunol.1000675","article-title":"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus","volume":"185","author":"Pilsczek","year":"2010","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nm.4294","article-title":"An emerging role for neutrophil extracellular traps in noninfectious disease","volume":"23","author":"Jorch","year":"2017","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/nm.2847","article-title":"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo","volume":"18","author":"Yipp","year":"2012","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1083\/jcb.97.2.368","article-title":"Functional activity of enucleated human polymorphonuclear leukocytes","volume":"97","author":"Roos","year":"1983","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Krishnamoorthy, N., Douda, D.N., Bruggemann, T.R., Ricklefs, I., Duvall, M.G., Abdulnour, R.E., Martinod, K., Tavares, L., Wang, X., and Cernadas, M. (2018). Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma. Sci. Immunol., 3.","DOI":"10.1126\/sciimmunol.aao4747"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/ni.2987","article-title":"Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens","volume":"15","author":"Branzk","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1073\/pnas.0900226106","article-title":"Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps","volume":"106","author":"Nascimento","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.micinf.2010.06.009","article-title":"NETs formed by human neutrophils inhibit growth of the pathogenic mold Aspergillus fumigatus","volume":"12","author":"McCormick","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.chom.2012.05.015","article-title":"Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1","volume":"12","author":"Saitoh","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.chom.2013.01.005","article-title":"Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps","volume":"13","author":"Jenne","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Saffarzadeh, M., Juenemann, C., Queisser, M.A., Lochnit, G., Barreto, G., Galuska, S.P., Lohmeyer, J., and Preissner, K.T. (2012). Neutrophil extracellular traps directly induce epithelial and endothelial cell death: A predominant role of histones. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032366"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/nm.2053","article-title":"Extracellular histones are major mediators of death in sepsis","volume":"15","author":"Xu","year":"2009","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1164\/rccm.201206-1037OC","article-title":"Circulating histones are mediators of trauma-associated lung injury","volume":"187","author":"Abrams","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1182\/blood-2010-05-287623","article-title":"von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models","volume":"117","author":"Brill","year":"2011","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/blood-2015-01-624023","article-title":"P-selectin promotes neutrophil extracellular trap formation in mice","volume":"126","author":"Etulain","year":"2015","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13464","DOI":"10.1038\/ncomms13464","article-title":"Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response","volume":"7","author":"Rossaint","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"Stark","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1182\/blood-2013-07-516484","article-title":"Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation","volume":"123","author":"Rossaint","year":"2014","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0092-8674(86)90735-X","article-title":"Inducible secretion of large, biologically potent von Willebrand factor multimers","volume":"46","author":"Sporn","year":"1986","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","article-title":"Neutrophil extracellular traps promote deep vein thrombosis in mice","volume":"10","author":"Brill","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA traps promote thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nm.2184","article-title":"Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases","volume":"16","author":"Massberg","year":"2010","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6819","DOI":"10.1074\/jbc.275.10.6819","article-title":"Cathepsin G activates protease-activated receptor-4 in human platelets","volume":"275","author":"Sambrano","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1182\/blood.2020007008","article-title":"Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome","volume":"136","author":"Middleton","year":"2020","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil extracellular traps in immunity and disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.4049\/jimmunol.1800159","article-title":"Intra- and Extracellular Degradation of Neutrophil Extracellular Traps by Macrophages and Dendritic Cells","volume":"203","author":"Lazzaretto","year":"2019","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Apel, F., Andreeva, L., Knackstedt, L.S., Streeck, R., Frese, C.K., Goosmann, C., Hopfner, K.P., and Zychlinsky, A. (2021). The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps. Sci. Signal., 14.","DOI":"10.1126\/scisignal.aax7942"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jaut.2015.08.018","article-title":"The responses of macrophages in interaction with neutrophils that undergo NETosis","volume":"67","author":"Nakazawa","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000480373","article-title":"Macrophage Extracellular Traps: A Scoping Review","volume":"10","author":"Doster","year":"2018","journal-title":"J. Innate Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nm.3547","article-title":"Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines","volume":"20","author":"Schauer","year":"2014","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.3389\/fimmu.2019.02176","article-title":"Aggregated NETs Sequester and Detoxify Extracellular Histones","volume":"10","author":"Knopf","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1096\/fj.201800752R","article-title":"Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases","volume":"33","author":"Hahn","year":"2019","journal-title":"FASEB J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S1050-1738(02)00233-5","article-title":"The role of ACE2 in cardiovascular physiology","volume":"13","author":"Oudit","year":"2003","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature17040","article-title":"Angiocrine functions of organ-specific endothelial cells","volume":"529","author":"Rafii","year":"2016","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Barnes, B.J., Adrover, J.M., Baxter-Stoltzfus, A., Borczuk, A., Cools-Lartigue, J., Crawford, J.M., Dassler-Plenker, J., Guerci, P., Huynh, C., and Knight, J.S. (2020). Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J. Exp. Med., 217.","DOI":"10.1084\/jem.20200652"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1093\/ajcp\/aqaa062","article-title":"COVID-19 Autopsies, Oklahoma, USA","volume":"153","author":"Barton","year":"2020","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"324","DOI":"10.7326\/L20-0895","article-title":"Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19","volume":"173","author":"Zhang","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101661","DOI":"10.1016\/j.berh.2021.101661","article-title":"The interplay between neutrophils, complement, and microthrombi in COVID-19","volume":"35","author":"Zuo","year":"2021","journal-title":"Best Pr. Res. Clin. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Veras, F.P., Pontelli, M.C., Silva, C.M., Toller-Kawahisa, J.E., de Lima, M., Nascimento, D.C., Schneider, A.H., Caetite, D., Tavares, L.A., and Paiva, I.M. (2020). SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology. J. Exp. Med., 217.","DOI":"10.1084\/jem.20201129"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22758","DOI":"10.1074\/jbc.M110.103275","article-title":"Elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete sites within the S2 domain","volume":"285","author":"Belouzard","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/jth.15179","article-title":"Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia","volume":"19","author":"Nicolai","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6151","DOI":"10.1172\/JCI141374","article-title":"Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis","volume":"130","author":"Skendros","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.4049\/jimmunol.2000644","article-title":"COVID-19: Complement, Coagulation, and Collateral Damage","volume":"205","author":"Lo","year":"2020","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/s41591-020-1021-2","article-title":"Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection","volume":"26","author":"Ramlall","year":"2020","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/CIRCULATIONAHA.120.048488","article-title":"Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated With Respiratory Failure and Coagulopathy","volume":"142","author":"Nicolai","year":"2020","journal-title":"Circulation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/ATVBAHA.117.309002","article-title":"Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition","volume":"37","author":"Pieterse","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1136\/annrheumdis-2018-213223","article-title":"Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)-dependent and NOX-independent pathways of neutrophil extracellular trap formation","volume":"77","author":"Pieterse","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1136\/annrheumdis-2013-204837","article-title":"Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2","volume":"74","author":"Zhao","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/jth.14844","article-title":"Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19","volume":"18","author":"Dolhnikoff","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41586-019-1167-6","article-title":"Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death","volume":"569","author":"Braster","year":"2019","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"S189","DOI":"10.1097\/01.inf.0000188196.87969.9a","article-title":"Respiratory syncytial virus infections: Old challenges and new opportunities","volume":"24","author":"Mejias","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/rmv.1704","article-title":"Respiratory syncytial virus infection and immunity","volume":"22","author":"Gonzalez","year":"2012","journal-title":"Rev. Med. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.micinf.2012.11.012","article-title":"Advances in understanding respiratory syncytial virus infection in airway epithelial cells and consequential effects on the immune response","volume":"15","author":"Lay","year":"2013","journal-title":"Microbes Infect."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.4049\/jimmunol.163.5.2816","article-title":"Respiratory syncytial virus stimulates neutrophil degranulation and chemokine release","volume":"163","author":"Jaovisidha","year":"1999","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.4049\/jimmunol.176.9.5529","article-title":"Respiratory syncytial virus inhibits granulocyte apoptosis through a phosphatidylinositol 3-kinase and NF-kappaB-dependent mechanism","volume":"176","author":"Lindemans","year":"2006","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/path.4660","article-title":"Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease","volume":"238","author":"Cortjens","year":"2016","journal-title":"J. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Funchal, G.A., Jaeger, N., Czepielewski, R.S., Machado, M.S., Muraro, S.P., Stein, R.T., Bonorino, C.B., and Porto, B.N. (2015). Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124082"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"14166","DOI":"10.1038\/s41598-018-32576-y","article-title":"Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through PAD-4 and necroptosis pathways activation","volume":"8","author":"Muraro","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.aogh.2015.08.014","article-title":"Treatment and Prevention of Pandemic H1N1 Influenza","volume":"81","author":"Rewar","year":"2015","journal-title":"Ann. Glob. Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0140-6736(17)30129-0","article-title":"Influenza","volume":"390","author":"Paules","year":"2017","journal-title":"Lancet"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Perrone, L.A., Plowden, J.K., Garcia-Sastre, A., Katz, J.M., and Tumpey, T.M. (2008). H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000115"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7441","DOI":"10.4049\/jimmunol.0902497","article-title":"Neutrophils ameliorate lung injury and the development of severe disease during influenza infection","volume":"183","author":"Tate","year":"2009","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1465-9921-9-57","article-title":"The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice","volume":"9","author":"Tate","year":"2008","journal-title":"Respir. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/mi.2017.1","article-title":"Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection","volume":"10","author":"Guo","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17732","DOI":"10.1038\/s41598-019-54053-w","article-title":"G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance","volume":"9","author":"Wang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1089\/vim.2006.0101","article-title":"CXCR2 is required for neutrophil recruitment to the lung during influenza virus infection, but is not essential for viral clearance","volume":"20","author":"Wareing","year":"2007","journal-title":"Viral. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1128\/JVI.01210-07","article-title":"Neutrophils play an essential role in cooperation with antibody in both protection against and recovery from pulmonary infection with influenza virus in mice","volume":"82","author":"Fujisawa","year":"2008","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Malachowa, N., Freedman, B., Sturdevant, D.E., Kobayashi, S.D., Nair, V., Feldmann, F., Starr, T., Steele-Mortimer, O., Kash, J.C., and Taubenberger, J.K. (2018). Differential Ability of Pandemic and Seasonal H1N1 Influenza A Viruses To Alter the Function of Human Neutrophils. mSphere, 3.","DOI":"10.1128\/mSphereDirect.00567-17"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2013.06.013","article-title":"A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection","volume":"154","author":"Brandes","year":"2013","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1038\/s41467-019-09607-x","article-title":"The role of platelets in mediating a response to human influenza infection","volume":"10","author":"Koupenova","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fcimb.2019.00108","article-title":"Neutrophils Induce a Novel Chemokine Receptors Repertoire During Influenza Pneumonia","volume":"9","author":"Rudd","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12931-020-01425-w","article-title":"Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses","volume":"21","author":"Chan","year":"2020","journal-title":"Respir. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/infdis\/jix475","article-title":"High Level of Neutrophil Extracellular Traps Correlates With Poor Prognosis of Severe Influenza A Infection","volume":"217","author":"Zhu","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajpath.2011.03.013","article-title":"Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis","volume":"179","author":"Narasaraju","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1086\/521027","article-title":"alpha-Defensin inhibits influenza virus replication by cell-mediated mechanism(s)","volume":"196","author":"Salvatore","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/00325481.2015.1074030","article-title":"Community-acquired pneumonia: An overview","volume":"127","author":"Mandell","year":"2015","journal-title":"Postgrad. Med."},{"key":"ref_101","first-page":"511","article-title":"Detection of aspiration of nasopharyngeal secretion and the relationship between the aspiration of nasopharyngeal secretion and the incidence of pneumonia","volume":"38","author":"Liu","year":"2015","journal-title":"Zhonghua Jie He He Hu Xi Za Zhi"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.4049\/jimmunol.0900688","article-title":"Human neutrophils kill Streptococcus pneumoniae via serine proteases","volume":"183","author":"Standish","year":"2009","journal-title":"J. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"10472","DOI":"10.1074\/jbc.M111.280321","article-title":"alpha-Enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps","volume":"287","author":"Mori","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1128\/IAI.00881-09","article-title":"The Streptococcus pneumoniae capsule inhibits complement activity and neutrophil phagocytosis by multiple mechanisms","volume":"78","author":"Hyams","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"19327","DOI":"10.18632\/oncotarget.8451","article-title":"Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia","volume":"7","author":"Moorthy","year":"2016","journal-title":"Oncotarget"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ebrahimi, F., Giaglis, S., Hahn, S., Blum, C.A., Baumgartner, C., Kutz, A., van Breda, S.V., Mueller, B., Schuetz, P., and Christ-Crain, M. (2018). Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: Secondary analysis of a randomised controlled trial. Eur. Respir. J., 51.","DOI":"10.1183\/13993003.01389-2017"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.cub.2006.01.056","article-title":"An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps","volume":"16","author":"Beiter","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Zhu, L., Kuang, Z., Wilson, B.A., and Lau, G.W. (2013). Competence-independent activity of pneumococcal EndA [corrected] mediates degradation of extracellular dna and nets and is important for virulence. PLoS ONE, 8.","DOI":"10.1371\/annotation\/75f51a45-a2de-4893-94cf-0045056a4d7c"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7985","DOI":"10.1038\/s41598-018-25865-z","article-title":"A novel extracellular vesicle-associated endodeoxyribonuclease helps Streptococcus pneumoniae evade neutrophil extracellular traps and is required for full virulence","volume":"8","author":"Jhelum","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.4049\/jimmunol.146.11.3922","article-title":"Degradation of cartilage matrix proteoglycan by human neutrophils involves both elastase and cathepsin G","volume":"146","author":"Janusz","year":"1991","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3389\/fmed.2018.00217","article-title":"The Role of Neutrophils and Neutrophil Elastase in Pulmonary Arterial Hypertension","volume":"5","author":"Taylor","year":"2018","journal-title":"Front. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"38013","DOI":"10.1038\/srep38013","article-title":"Streptococcus pneumoniae disrupts pulmonary immune defence via elastase release following pneumolysin-dependent neutrophil lysis","volume":"6","author":"Domon","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"L1145","DOI":"10.1152\/ajplung.00039.2015","article-title":"Collagen and elastin cross-linking is altered during aberrant late lung development associated with hyperoxia","volume":"308","author":"Mizikova","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.chest.2017.03.056","article-title":"The Role of Neutrophil Elastase Inhibitors in Lung Diseases","volume":"152","author":"Polverino","year":"2017","journal-title":"Chest"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2796.2005.01476.x","article-title":"Neutrophil serine proteases: Potential key regulators of cell signalling during inflammation","volume":"257","author":"Wiedow","year":"2005","journal-title":"J. Intern. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.4049\/jimmunol.1301920","article-title":"Mechanism of neutrophil dysfunction: Neutrophil serine proteases cleave and inactivate the C5a receptor","volume":"192","author":"Tambourgi","year":"2014","journal-title":"J. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"732","DOI":"10.3389\/fimmu.2018.00732","article-title":"Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-Like Receptors and Cytokines in Pneumococcal Pneumonia","volume":"9","author":"Domon","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1016\/j.celrep.2018.02.062","article-title":"Extracellular Neutrophil Proteases Are Efficient Regulators of IL-1, IL-33, and IL-36 Cytokine Activity but Poor Effectors of Microbial Killing","volume":"22","author":"Clancy","year":"2018","journal-title":"Cell Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1038\/s41598-021-82212-5","article-title":"Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia","volume":"11","author":"Domon","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2119\/molmed.2009.00109","article-title":"Human neutrophil elastase-mediated cleavage sites of MMP-9 and TIMP-1: Implications to cystic fibrosis proteolytic dysfunction","volume":"16","author":"Jackson","year":"2010","journal-title":"Mol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1111\/j.1462-5822.2006.00857.x","article-title":"Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps","volume":"9","author":"Wartha","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/cid\/ciw300","article-title":"Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes","volume":"63","author":"Self","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jcv.2016.04.008","article-title":"Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013\u20132014","volume":"80","author":"Shah","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1074\/mcp.O116.065581","article-title":"Using Quantitative Spectrometry to Understand the Influence of Genetics and Nutritional Perturbations On the Virulence Potential of Staphylococcus aureus","volume":"16","author":"Chapman","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1073\/pnas.1115006109","article-title":"How Staphylococcus aureus biofilms develop their characteristic structure","volume":"109","author":"Periasamy","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Grousd, J.A., Rich, H.E., and Alcorn, J.F. (2019). Host-Pathogen Interactions in Gram-Positive Bacterial Pneumonia. Clin. Microbiol. Rev., 32.","DOI":"10.1128\/CMR.00107-18"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jaci.2007.06.005","article-title":"Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets","volume":"120","author":"Nizet","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.tim.2005.10.002","article-title":"Staphylococcal innate immune evasion","volume":"13","author":"Rooijakkers","year":"2005","journal-title":"Trends Microbiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1574-6968.2006.00229.x","article-title":"Clumping factor A of Staphylococcus aureus inhibits phagocytosis by human polymorphonuclear leucocytes","volume":"258","author":"Higgins","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"52789","DOI":"10.1074\/jbc.M410698200","article-title":"Insight of host immune evasion mediated by two variants of group a Streptococcus Mac protein","volume":"279","author":"Agniswamy","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/lam.12438","article-title":"alpha-Defensins partially protect human neutrophils against Panton-Valentine leukocidin produced by Staphylococcus aureus","volume":"61","author":"Casalegno","year":"2015","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1159\/000319909","article-title":"Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps","volume":"2","author":"Berends","year":"2010","journal-title":"J. Innate Immun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1126\/science.1242255","article-title":"Staphylococcus aureus degrades neutrophil extracellular traps to promote immune cell death","volume":"342","author":"Thammavongsa","year":"2013","journal-title":"Science"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Lefrancais, E., Mallavia, B., Zhuo, H., Calfee, C.S., and Looney, M.R. (2018). Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. Jci Insight, 3.","DOI":"10.1172\/jci.insight.98178"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Sultan, A.R., Swierstra, J.W., Lemmens-den Toom, N.A., Snijders, S.V., Hansenova Manaskova, S., Verbon, A., and van Wamel, W.J.B. (2018). Production of Staphylococcal Complement Inhibitor (SCIN) and Other Immune Modulators during the Early Stages of Staphylococcus aureus Biofilm Formation in a Mammalian Cell Culture Medium. Infect. Immun., 86.","DOI":"10.1128\/IAI.00352-18"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Sultan, A.R., Hoppenbrouwers, T., Lemmens-den Toom, N.A., Snijders, S.V., van Neck, J.W., Verbon, A., de Maat, M.P.M., and van Wamel, W.J.B. (2019). During the Early Stages of Staphylococcus aureus Biofilm Formation, Induced Neutrophil Extracellular Traps Are Degraded by Autologous Thermonuclease. Infect. Immun., 87.","DOI":"10.1128\/IAI.00605-19"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"7416","DOI":"10.1073\/pnas.1721949115","article-title":"Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing","volume":"115","author":"Bhattacharya","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.3389\/fimmu.2019.02552","article-title":"High Nuclease Activity of Long Persisting Staphylococcus aureus Isolates Within the Airways of Cystic Fibrosis Patients Protects Against NET-Mediated Killing","volume":"10","author":"Herzog","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMe020070","article-title":"What is cystic fibrosis?","volume":"347","author":"Knowles","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1136\/thoraxjnl-2011-200585","article-title":"Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis","volume":"67","author":"Regamey","year":"2012","journal-title":"Thorax"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3390\/pathogens4010066","article-title":"Bacterial Adaptation during Chronic Respiratory Infections","volume":"4","author":"Cullen","year":"2015","journal-title":"Pathogens"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.imlet.2014.03.003","article-title":"NET formation induced by Pseudomonas aeruginosa cystic fibrosis isolates measured as release of myeloperoxidase-DNA and neutrophil elastase-DNA complexes","volume":"160","author":"Yoo","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4728","DOI":"10.4049\/jimmunol.1301589","article-title":"Release of cystic fibrosis airway inflammatory markers from Pseudomonas aeruginosa-stimulated human neutrophils involves NADPH oxidase-dependent extracellular DNA trap formation","volume":"192","author":"Yoo","year":"2014","journal-title":"J. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1517\/14728222.12.2.145","article-title":"Targeting neutrophil elastase in cystic fibrosis","volume":"12","author":"Kelly","year":"2008","journal-title":"Expert Opin. Targets"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"a009738","DOI":"10.1101\/cshperspect.a009738","article-title":"The cystic fibrosis airway microbiome","volume":"3","author":"Lynch","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1136\/thoraxjnl-2017-210134","article-title":"Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis","volume":"73","author":"Gray","year":"2018","journal-title":"Thorax"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1136\/thx.2008.096834","article-title":"Prolonged survival of neutrophils from patients with Delta F508 CFTR mutations","volume":"63","author":"McKeon","year":"2008","journal-title":"Thorax"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jcf.2011.09.008","article-title":"Ultrastructural characterization of cystic fibrosis sputum using atomic force and scanning electron microscopy","volume":"11","author":"Manzenreiter","year":"2012","journal-title":"J. Cyst. Fibros."},{"key":"ref_150","first-page":"104","article-title":"Understanding the Entanglement: Neutrophil Extracellular Traps (NETs) in Cystic Fibrosis","volume":"7","author":"Gonzalez","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Papayannopoulos, V., Staab, D., and Zychlinsky, A. (2011). Neutrophil elastase enhances sputum solubilization in cystic fibrosis patients receiving DNase therapy. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028526"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1165\/rcmb.2011-0380OC","article-title":"Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum","volume":"47","author":"Dubois","year":"2012","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"408935","DOI":"10.1155\/2015\/408935","article-title":"Free DNA in cystic fibrosis airway fluids correlates with airflow obstruction","volume":"2015","author":"Marcos","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_154","first-page":"907","article-title":"Degradation of endothelial cell matrix heparan sulfate proteoglycan by elastase and the myeloperoxidase-H2O2-chloride system","volume":"143","author":"Klebanoff","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.4049\/jimmunol.1300436","article-title":"Macrophage clearance of neutrophil extracellular traps is a silent process","volume":"191","author":"Farrera","year":"2013","journal-title":"J. Immunol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/ncb1456","article-title":"CFTR regulates phagosome acidification in macrophages and alters bactericidal activity","volume":"8","author":"Di","year":"2006","journal-title":"Nat. Cell. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Young, R.L., Malcolm, K.C., Kret, J.E., Caceres, S.M., Poch, K.R., Nichols, D.P., Taylor-Cousar, J.L., Saavedra, M.T., Randell, S.H., and Vasil, M.L. (2011). Neutrophil extracellular trap (NET)-mediated killing of Pseudomonas aeruginosa: Evidence of acquired resistance within the CF airway, independent of CFTR. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023637"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Mulcahy, H., Charron-Mazenod, L., and Lewenza, S. (2008). Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000213"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1189\/jlb.0511260","article-title":"Sialoglycoproteins adsorbed by Pseudomonas aeruginosa facilitate their survival by impeding neutrophil extracellular trap through siglec-9","volume":"91","author":"Khatua","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"12333","DOI":"10.1021\/es402925k","article-title":"A cantilever biosensor-based assay for toxin-producing cyanobacteria Microcystis aeruginosa using 16S rRNA","volume":"47","author":"Johnson","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1128\/JB.05230-11","article-title":"Surface-localized spermidine protects the Pseudomonas aeruginosa outer membrane from antibiotic treatment and oxidative stress","volume":"194","author":"Johnson","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Halverson, T.W., Wilton, M., Poon, K.K., Petri, B., and Lewenza, S. (2015). DNA is an antimicrobial component of neutrophil extracellular traps. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004593"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/S0140-6736(17)31222-9","article-title":"Chronic obstructive pulmonary disease","volume":"389","author":"Rabe","year":"2017","journal-title":"Lancet"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1056\/NEJM198910053211402","article-title":"The effect of cigarette smoking on neutrophil kinetics in human lungs","volume":"321","author":"MacNee","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.jaci.2006.12.640","article-title":"The neutrophil in chronic obstructive pulmonary disease","volume":"119","author":"Quint","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1136\/thx.2009.113647","article-title":"Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD","volume":"64","author":"Caramori","year":"2009","journal-title":"Thorax"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1164\/ajrccm.163.2.2003122","article-title":"Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease","volume":"163","author":"Aaron","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1056\/NEJMoa032158","article-title":"The nature of small-airway obstruction in chronic obstructive pulmonary disease","volume":"350","author":"Hogg","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1378\/chest.123.4.1240","article-title":"Neutrophil chemotactic activity of sputum from patients with COPD: Role of interleukin 8 and leukotriene B4","volume":"123","author":"Beeh","year":"2003","journal-title":"Chest"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1164\/rccm.200208-794OC","article-title":"Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease","volume":"168","author":"Qiu","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2174\/156801005774912806","article-title":"Inflammatory mediators in chronic obstructive pulmonary disease","volume":"4","author":"Chung","year":"2005","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.rmed.2015.08.008","article-title":"Neutrophil extracellular trap formation and extracellular DNA in sputum of stable COPD patients","volume":"109","author":"Pedersen","year":"2015","journal-title":"Respir. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/resp.12730","article-title":"Neutrophil extracellular traps are associated with inflammation in chronic airway disease","volume":"21","author":"Wright","year":"2016","journal-title":"Respirology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12931-015-0221-7","article-title":"Neutrophil extracellular trap (NET) formation characterises stable and exacerbated COPD and correlates with airflow limitation","volume":"16","author":"Obermayer","year":"2015","journal-title":"Respir. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jaci.2017.04.022","article-title":"Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease","volume":"141","author":"Dicker","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2147\/COPD.S121389","article-title":"Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: A population database study using linked health care records","volume":"12","author":"Williams","year":"2017","journal-title":"Int. J. Chron. Obs. Pulmon. Dis."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Trivedi, A., Khan, M.A., Bade, G., and Talwar, A. (2021). Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010053"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1128\/CMR.12.2.310","article-title":"Aspergillus fumigatus and aspergillosis","volume":"12","author":"Latge","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1097\/01.mcp.0000219272.57933.01","article-title":"Fungal respiratory disease","volume":"12","author":"Yao","year":"2006","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1469-0691.2011.03681.x","article-title":"Immunotherapy of aspergillosis","volume":"18","author":"Carvalho","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.idc.2006.07.001","article-title":"Cryptococcosis","volume":"20","author":"Chayakulkeeree","year":"2006","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrmicro2522","article-title":"Expanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box","volume":"9","author":"Kronstad","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1128\/CMR.8.4.515","article-title":"Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans","volume":"8","author":"Mitchell","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1056\/NEJM200409163511222","article-title":"Pneumocystis pneumonia","volume":"351","author":"Udwadia","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/jac\/43.3.321","article-title":"Endemic mycoses: A treatment update","volume":"43","author":"Lortholary","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1128\/CMR.8.1.146","article-title":"Endemic mycoses in AIDS: A clinical review","volume":"8","author":"Wheat","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3314\/mmj.52.193","article-title":"The genus Aspergillus","volume":"52","author":"Yaguchi","year":"2011","journal-title":"Med. Mycol. J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1086\/600380","article-title":"Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection","volume":"200","author":"Mircescu","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1128\/IAI.71.2.891-903.2003","article-title":"Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages","volume":"71","author":"Philippe","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/mmy.40.5.455.464","article-title":"Molecular characterization of a cell wall-associated beta(1-3)endoglucanase of Aspergillus fumigatus","volume":"40","author":"Mouyna","year":"2002","journal-title":"Med. Mycol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1099\/00221287-148-9-2819","article-title":"Characterization of a cell-wall acid phosphatase (PhoAp) in Aspergillus fumigatus","volume":"148","author":"Bernard","year":"2002","journal-title":"Microbiology"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S0966-842X(01)02104-7","article-title":"The pathobiology of Aspergillus fumigatus","volume":"9","author":"Latge","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Bruns, S., Kniemeyer, O., Hasenberg, M., Aimanianda, V., Nietzsche, S., Thywissen, A., Jeron, A., Latge, J.P., Brakhage, A.A., and Gunzer, M. (2010). Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000873"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1084\/jem.20061301","article-title":"The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps","volume":"204","author":"Jaillon","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1128\/IAI.00096-14","article-title":"NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis","volume":"82","author":"Rohm","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"151867","DOI":"10.1016\/j.imbio.2019.11.002","article-title":"Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis","volume":"225","author":"Alflen","year":"2020","journal-title":"Immunobiology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/imr.12454","article-title":"How neutrophils kill fungi","volume":"273","author":"Gazendam","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.4049\/jimmunol.1501811","article-title":"Human Neutrophils Use Different Mechanisms To Kill Aspergillus fumigatus Conidia and Hyphae: Evidence from Phagocyte Defects","volume":"196","author":"Gazendam","year":"2016","journal-title":"J. Immunol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1172\/JCI2301","article-title":"Virulence of catalase-deficient aspergillus nidulans in p47(phox)-\/- mice. Implications for fungal pathogenicity and host defense in chronic granulomatous disease","volume":"101","author":"Chang","year":"1998","journal-title":"J. Clin. Invest."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1084\/jem.185.2.207","article-title":"Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus","volume":"185","author":"Morgenstern","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1128\/IAI.00921-10","article-title":"Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms","volume":"79","author":"Henriet","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1182\/blood-2009-05-221606","article-title":"Restoration of NET formation by gene therapy in CGD controls aspergillosis","volume":"114","author":"Bianchi","year":"2009","journal-title":"Blood"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.jaci.2011.01.021","article-title":"Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent","volume":"127","author":"Bianchi","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1462-5822.2009.01409.x","article-title":"In vivo biofilm composition of Aspergillus fumigatus","volume":"12","author":"Loussert","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Fontaine, T., Delangle, A., Simenel, C., Coddeville, B., van Vliet, S.J., van Kooyk, Y., Bozza, S., Moretti, S., Schwarz, F., and Trichot, C. (2011). Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002372"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"e00252-16","DOI":"10.1128\/mBio.00252-16","article-title":"Deacetylation of Fungal Exopolysaccharide Mediates Adhesion and Biofilm Formation","volume":"7","author":"Lee","year":"2016","journal-title":"mBio"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Gravelat, F.N., Beauvais, A., Liu, H., Lee, M.J., Snarr, B.D., Chen, D., Xu, W., Kravtsov, I., Hoareau, C.M., and Vanier, G. (2013). Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal beta-glucan from the immune system. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003575"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Lee, M.J., Liu, H., Barker, B.M., Snarr, B.D., Gravelat, F.N., Al Abdallah, Q., Gavino, C., Baistrocchi, S.R., Ostapska, H., and Xiao, T. (2015). The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005187"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1378\/chest.120.1.203","article-title":"Efficacy of recombinant human deoxyribonuclease I in the hospital management of respiratory syncytial virus bronchiolitis","volume":"120","author":"Nasr","year":"2001","journal-title":"Chest"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/ppul.10348","article-title":"Dornase alfa in the treatment of cystic fibrosis in Europe: A report from the Epidemiologic Registry of Cystic Fibrosis","volume":"36","author":"Hodson","year":"2003","journal-title":"Pediatr. Pulmonol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1080\/08035250600752466","article-title":"Effect of aerosolized rhDNase (Pulmozyme) on pulmonary colonization in patients with cystic fibrosis","volume":"95","author":"Frederiksen","year":"2006","journal-title":"Acta Paediatr."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s10020-020-00215-w","article-title":"Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series","volume":"26","author":"Weber","year":"2020","journal-title":"Mol. Med."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1186\/s13063-020-04488-8","article-title":"Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): A structured summary of a study protocol for a randomised controlled trial","volume":"21","author":"Desilles","year":"2020","journal-title":"Trials"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"107602","DOI":"10.1016\/j.celrep.2020.107602","article-title":"Histones, DNA, and Citrullination Promote Neutrophil Extracellular Trap Inflammation by Regulating the Localization and Activation of TLR4","volume":"31","author":"Tsourouktsoglou","year":"2020","journal-title":"Cell Rep."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1164\/rccm.201604-0712OC","article-title":"Antihistone Properties of C1 Esterase Inhibitor Protect against Lung Injury","volume":"196","author":"Wygrecka","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s41423-020-0381-3","article-title":"Therapeutic ACPA inhibits NET formation: A potential therapy for neutrophil-mediated inflammatory diseases","volume":"18","author":"Chirivi","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_219","first-page":"91","article-title":"C1-Esterase inhibitor: An anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema","volume":"52","author":"Caliezi","year":"2000","journal-title":"Pharm. Rev."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.4049\/jimmunol.171.5.2594","article-title":"C1 inhibitor prevents endotoxin shock via a direct interaction with lipopolysaccharide","volume":"171","author":"Liu","year":"2003","journal-title":"J. Immunol."},{"key":"ref_221","first-page":"529","article-title":"Administration of C1 inhibitor reduces neutrophil activation in patients with sepsis","volume":"10","author":"Zeerleder","year":"2003","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1097\/CCM.0b013e318236edb8","article-title":"C1-esterase inhibitor infusion increases survival rates for patients with sepsis*","volume":"40","author":"Igonin","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.3389\/fimmu.2019.02957","article-title":"Citrullinated Histone H3 as a Therapeutic Target for Endotoxic Shock in Mice","volume":"10","author":"Deng","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.pupt.2004.12.013","article-title":"Sivelestat, a specific neutrophil elastase inhibitor, prevented phorbol myristate acetate-induced acute lung injury in conscious rabbits","volume":"18","author":"Hagio","year":"2005","journal-title":"Pulm. Pharm."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00540-005-0362-9","article-title":"Clinical effects of a neutrophil elastase inhibitor, sivelestat, in patients with acute respiratory distress syndrome","volume":"20","author":"Okayama","year":"2006","journal-title":"J. Anesth."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.pupt.2004.05.003","article-title":"Relationship between neutrophil elastase and acute lung injury in humans","volume":"17","author":"Tamakuma","year":"2004","journal-title":"Pulm. Pharm."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1440-1843.2008.01283.x","article-title":"Neutrophil elastase activity in acute lung injury and respiratory distress syndrome","volume":"13","author":"Hashimoto","year":"2008","journal-title":"Respirology"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s40560-014-0067-y","article-title":"Effect of a selective neutrophil elastase inhibitor on mortality and ventilator-free days in patients with increased extravascular lung water: A post hoc analysis of the PiCCO Pulmonary Edema Study","volume":"2","author":"Tagami","year":"2014","journal-title":"J. Intensive Care"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2147\/DDDT.S42004","article-title":"Usefulness of a selective neutrophil elastase inhibitor, sivelestat, in acute lung injury patients with sepsis","volume":"7","author":"Miyoshi","year":"2013","journal-title":"Drug Des. Devel."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1124\/jpet.112.202879","article-title":"Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs","volume":"345","author":"Lapponi","year":"2013","journal-title":"J. Pharm. Exp."},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Hirose, T., Hamaguchi, S., Matsumoto, N., Irisawa, T., Seki, M., Tasaki, O., Hosotsubo, H., Yamamoto, N., Yamamoto, K., and Akeda, Y. (2014). Presence of neutrophil extracellular traps and citrullinated histone H3 in the bloodstream of critically ill patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111755"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1124\/mol.113.089821","article-title":"Novel small molecule inhibitors of TLR7 and TLR9: Mechanism of action and efficacy in vivo","volume":"85","author":"Lamphier","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00592-018-1129-8","article-title":"The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo","volume":"55","author":"Menegazzo","year":"2018","journal-title":"Acta Diabetol."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Gregoire, M., Uhel, F., Lesouhaitier, M., Gacouin, A., Guirriec, M., Mourcin, F., Dumontet, E., Chalin, A., Samson, M., and Berthelot, L.L. (2018). Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS. Eur. Respir. J., 52.","DOI":"10.1183\/13993003.02590-2017"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12931-017-0689-4","article-title":"Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma","volume":"18","author":"Vargas","year":"2017","journal-title":"Respir. Res."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1172\/JCI83873","article-title":"Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation","volume":"126","author":"Yost","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/1465-9921-14-137","article-title":"Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist","volume":"14","author":"Leaker","year":"2013","journal-title":"Respir. Res."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41467-018-02896-8","article-title":"A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense","volume":"9","author":"Wolf","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41418-018-0261-x","article-title":"To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps","volume":"26","author":"Boeltz","year":"2019","journal-title":"Cell Death Differ."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/1932\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:37:00Z","timestamp":1760164620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/1932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":239,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cells10081932"],"URL":"https:\/\/doi.org\/10.3390\/cells10081932","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]}}}