{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:26:11Z","timestamp":1776273971526,"version":"3.50.1"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001448","name":"Alpha-1 Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001448","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001448","name":"Alpha-1 Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001448","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Pulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, were positively correlated with sign of endothelial damage in those patients as determined by plasma levels of LDH. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0274427","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T16:56:03Z","timestamp":1662742563000},"page":"e0274427","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Correlation of alpha-1 antitrypsin levels and exosome associated neutrophil elastase endothelial injury in subjects with SARS-CoV2 infection"],"prefix":"10.1371","volume":"17","author":[{"given":"Jorge","family":"Lascano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Oshins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Eagan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zerka","family":"Wadood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Qiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammy","family":"Flagg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yogesh","family":"Scindia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-065X","authenticated-orcid":true,"given":"Borna","family":"Mehrad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Brantly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-1622","authenticated-orcid":true,"given":"Nazli","family":"Khodayari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"pone.0274427.ref001","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/aas.12001","article-title":"Acute respiratory distress syndrome: nationwide changes in incidence, treatment and mortality over 23 years","volume":"57","author":"MI Sigurdsson","year":"2013","journal-title":"Acta Anaesthesiol Scand"},{"key":"pone.0274427.ref002","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan","volume":"395","author":"C Huang","year":"2020","journal-title":"China. Lancet"},{"key":"pone.0274427.ref003","article-title":"Targeting potential drivers of COVID-19: Neutrophil extracellular traps","author":"BJ Barnes","year":"2020","journal-title":"J Exp Med"},{"key":"pone.0274427.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/thoraxjnl-2016-209170","article-title":"What drives neutrophils to the alveoli in ARDS?","volume":"72","author":"RL Zemans","year":"2017","journal-title":"Thorax"},{"key":"pone.0274427.ref005","article-title":"Understanding the role of neutrophils in acute respiratory distress syndrome","author":"SC Yang","year":"2020","journal-title":"Biomed J"},{"key":"pone.0274427.ref006","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":"E Polverino","year":"2017","journal-title":"Chest"},{"key":"pone.0274427.ref007","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: specific regulators of inflammation","volume":"6","author":"CT Pham","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"pone.0274427.ref008","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1083\/jcb.131.3.775","article-title":"Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases","volume":"131","author":"CA Owen","year":"1995","journal-title":"J Cell Biol"},{"key":"pone.0274427.ref009","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":"T Tagami","year":"2014","journal-title":"J Intensive Care"},{"key":"pone.0274427.ref010","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3109\/01902148.2011.633306","article-title":"Administration of a specific inhibitor of neutrophil elastase attenuates pulmonary fibrosis after acute lung injury in mice","volume":"38","author":"N Fujino","year":"2012","journal-title":"Exp Lung Res"},{"key":"pone.0274427.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(02)02182-9","article-title":"The role of neutrophil elastase in acute lung injury","volume":"451","author":"K Kawabata","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"pone.0274427.ref012","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1056\/NEJM198101223040402","article-title":"Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome","volume":"304","author":"CT Lee","year":"1981","journal-title":"N Engl J Med"},{"key":"pone.0274427.ref013","doi-asserted-by":"crossref","first-page":"e0172983","DOI":"10.1371\/journal.pone.0172983","article-title":"SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78","volume":"12","author":"N Khodayari","year":"2017","journal-title":"PLoS One"},{"key":"pone.0274427.ref014","doi-asserted-by":"crossref","first-page":"15007","DOI":"10.1073\/pnas.1309648110","article-title":"Anti-inflammatory and immunomodulatory properties of alpha1-antitrypsin without inhibition of elastase","volume":"110","author":"D Jonigk","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0274427.ref015","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1515\/bchm3.1994.375.10.659","article-title":"Comparison of properties of membrane bound versus soluble forms of human leukocytic elastase and cathepsin G","volume":"375","author":"N Bangalore","year":"1994","journal-title":"Biol Chem Hoppe Seyler"},{"key":"pone.0274427.ref016","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cell.2018.12.002","article-title":"Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung","volume":"176","author":"KR Genschmer","year":"2019","journal-title":"Cell"},{"key":"pone.0274427.ref017","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12964-020-00648-0","article-title":"Alpha-1 antitrypsin deficient individuals have circulating extracellular vesicles with profibrogenic cargo","volume":"18","author":"N Khodayari","year":"2020","journal-title":"Cell Commun Signal"},{"key":"pone.0274427.ref018","doi-asserted-by":"crossref","first-page":"e0228871","DOI":"10.1371\/journal.pone.0228871","article-title":"Variability in protein cargo detection in technical and biological replicates of exosome-enriched extracellular vesicles","volume":"15","author":"S Tiruvayipati","year":"2020","journal-title":"PLoS One"},{"key":"pone.0274427.ref019","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"R Kalluri","year":"2020","journal-title":"Science"},{"key":"pone.0274427.ref020","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.stemcr.2014.04.006","article-title":"Exosomes as critical agents of cardiac regeneration triggered by cell therapy","volume":"2","author":"AG Ibrahim","year":"2014","journal-title":"Stem Cell Reports"},{"key":"pone.0274427.ref021","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20200551","article-title":"Elongated neutrophil-derived structures are blood-borne microparticles formed by rolling neutrophils during sepsis","volume":"218","author":"A Marki","year":"2021","journal-title":"J Exp Med"},{"key":"pone.0274427.ref022","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1172\/JCI112426","article-title":"Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase","volume":"77","author":"LA Smedly","year":"1986","journal-title":"J Clin Invest"},{"key":"pone.0274427.ref023","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1164\/rccm.202006-2598LE","article-title":"COVID-19-associated Acute Respiratory Distress Syndrome Clarified: A Vascular Endotype?","volume":"202","author":"NS Mangalmurti","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0274427.ref024","doi-asserted-by":"crossref","first-page":"152001","DOI":"10.1016\/j.imbio.2020.152001","article-title":"Endothelial injury and thrombotic microangiopathy in COVID-19: Treatment with the lectin-pathway inhibitor narsoplimab","volume":"225","author":"A Rambaldi","year":"2020","journal-title":"Immunobiology"},{"key":"pone.0274427.ref025","first-page":"259","article-title":"Endothelial activation and injury by cigarette smoke exposure","volume":"25","author":"F Guarino","year":"2011","journal-title":"J Biol Regul Homeost Agents"},{"key":"pone.0274427.ref026","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1177\/2045893217702346","article-title":"A high-yield isolation and enrichment strategy for human lung microvascular endothelial cells","volume":"7","author":"C Gaskill","year":"2017","journal-title":"Pulm Circ"},{"key":"pone.0274427.ref027","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.femsyr.2005.03.005","article-title":"Production, purification and characterisation of recombinant Fahsin, a novel antistasin-type proteinase inhibitor","volume":"5","author":"EC de Bruin","year":"2005","journal-title":"FEMS Yeast Res"},{"key":"pone.0274427.ref028","doi-asserted-by":"crossref","first-page":"560141","DOI":"10.1155\/2013\/560141","article-title":"Intracellular secretory leukoprotease inhibitor modulates inositol 1,4,5-triphosphate generation and exerts an anti-inflammatory effect on neutrophils of individuals with cystic fibrosis and chronic obstructive pulmonary disease","volume":"2013","author":"EP Reeves","year":"2013","journal-title":"Biomed Res Int"},{"key":"pone.0274427.ref029","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"pone.0274427.ref030","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cca.2020.06.012","article-title":"Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients","volume":"509","author":"E Poggiali","year":"2020","journal-title":"Clin Chim Acta"},{"key":"pone.0274427.ref031","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3855\/jidc.14072","article-title":"Diagnostic and early prognostic value of serum CRP and LDH levels in patients with possible COVID-19 at the first admission","volume":"15","author":"D Akdogan","year":"2021","journal-title":"J Infect Dev Ctries"},{"key":"pone.0274427.ref032","doi-asserted-by":"crossref","first-page":"100338","DOI":"10.1016\/j.aohep.2021.100338","article-title":"Lactate-dehydrogenase associated with mortality in hospitalized patients with COVID-19 in Mexico: a multi-centre retrospective cohort study","volume":"24","author":"P Vidal-Cevallos","year":"2021","journal-title":"Ann Hepatol"},{"key":"pone.0274427.ref033","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s12877-022-03059-7","article-title":"Prognostic value of neutrophile-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) levels for geriatric patients with COVID-19","volume":"22","author":"U Onal","year":"2022","journal-title":"BMC Geriatr"},{"key":"pone.0274427.ref034","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1074\/jbc.RA118.006142","article-title":"Modulation of calreticulin expression reveals a novel exosome-mediated mechanism of Z variant alpha1-antitrypsin disposal","volume":"294","author":"N Khodayari","year":"2019","journal-title":"J Biol Chem"},{"key":"pone.0274427.ref035","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1164\/rccm.202005-1583OC","article-title":"Characterization of the Inflammatory Response to Severe COVID-19 Illness","volume":"202","author":"OJ McElvaney","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0274427.ref036","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/MOH.0000000000000001","article-title":"The potential of neutrophil elastase inhibitors as anti-inflammatory therapies","volume":"21","author":"PA Henriksen","year":"2014","journal-title":"Curr Opin Hematol"},{"key":"pone.0274427.ref037","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3109\/15412555.2013.764403","article-title":"Neutrophil elastase-mediated lung disease","volume":"101","author":"RA Sandhaus","year":"2013","journal-title":"COPD"},{"key":"pone.0274427.ref038","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01910-2017","article-title":"Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis","volume":"51","author":"AS Dittrich","year":"2018","journal-title":"Eur Respir J"},{"key":"pone.0274427.ref039","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1080\/15412555.2017.1401600","article-title":"The Effects of Inflammation on Alpha 1 Antitrypsin Levels in a National Screening Cohort","volume":"15","author":"CL Sanders","year":"2018","journal-title":"COPD"},{"key":"pone.0274427.ref040","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s11658-020-00228-7","article-title":"The usefulness of lactate dehydrogenase measurements in current oncological practice","volume":"25","author":"A Forkasiewicz","year":"2020","journal-title":"Cell Mol Biol Lett"},{"key":"pone.0274427.ref041","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1378\/chest.100.4.1182-b","article-title":"Serum lactate dehydrogenase in interstitial lung disease","volume":"100","author":"RG McFadden","year":"1991","journal-title":"Chest"},{"key":"pone.0274427.ref042","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1111\/all.14746","article-title":"Elastase and exacerbation of neutrophil innate immunity are involved in multi-visceral manifestations of COVID-19","volume":"76","author":"JL Gueant","year":"2021","journal-title":"Allergy"},{"key":"pone.0274427.ref043","doi-asserted-by":"crossref","first-page":"48487","DOI":"10.1074\/jbc.R400025200","article-title":"C-reactive Protein","volume":"279","author":"S Black","year":"2004","journal-title":"J Biol Chem"},{"key":"pone.0274427.ref044","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0092-8674(91)90174-W","article-title":"Selectins: a family of adhesion receptors","volume":"67","author":"M Bevilacqua","year":"1991","journal-title":"Cell"},{"key":"pone.0274427.ref045","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/0167-5699(93)90267-O","article-title":"Circulating adhesion molecules in disease","volume":"14","author":"AJ Gearing","year":"1993","journal-title":"Immunol Today"},{"key":"pone.0274427.ref046","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00441-013-1779-3","article-title":"PECAM-1: regulator of endothelial junctional integrity","volume":"355","author":"JR Privratsky","year":"2014","journal-title":"Cell Tissue Res"},{"key":"pone.0274427.ref047","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1186\/cc13754","article-title":"Soluble platelet-endothelial cell adhesion molecule-1, a biomarker of ventilator-induced lung injury","volume":"18","author":"J Villar","year":"2014","journal-title":"Crit Care"},{"key":"pone.0274427.ref048","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jhep.2013.12.022","article-title":"MMP-9 deficiency shelters endothelial PECAM-1 expression and enhances regeneration of steatotic livers after ischemia and reperfusion injury","volume":"60","author":"H Kato","year":"2014","journal-title":"J Hepatol"},{"key":"pone.0274427.ref049","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-5793(96)01508-6","article-title":"Activation of MMP-9 by neutrophil elastase in an in vivo model of acute lung injury","volume":"402","author":"G Ferry","year":"1997","journal-title":"FEBS Lett"},{"key":"pone.0274427.ref050","first-page":"1158","article-title":"[The role of tissue factor and tissue factor pathway inhibitor in blood coagulation and in thrombotic complications]","volume":"68","author":"M Kotschy","year":"2010","journal-title":"Kardiol Pol"},{"key":"pone.0274427.ref051","doi-asserted-by":"crossref","first-page":"442","DOI":"10.5114\/ada.2019.87447","article-title":"Evaluation of plasma levels of tissue factor and tissue factor pathway inhibitor in patients with psoriasis","volume":"36","author":"A Domagala","year":"2019","journal-title":"Postepy Dermatol Alergol"},{"key":"pone.0274427.ref052","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/jth.15660","article-title":"Non-severe COVID-19 is associated with endothelial damage and hypercoagulability despite pharmacological thromboprophylaxis","volume":"20","author":"S Kelliher","year":"2022","journal-title":"J Thromb Haemost"},{"key":"pone.0274427.ref053","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5551\/jat1994.4.135","article-title":"The role of tissue factor in the pathogenesis of thrombosis and atherosclerosis","volume":"4","author":"Y Asada","year":"1998","journal-title":"J Atheroscler Thromb"},{"key":"pone.0274427.ref054","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1152\/jappl.1986.61.6.2224","article-title":"O2 metabolites and neutrophil elastase synergistically cause edematous injury in isolated rat lungs","volume":"61","author":"BR Baird","year":"1986","journal-title":"J Appl Physiol (1985"},{"key":"pone.0274427.ref055","first-page":"H1947","article-title":"Protease inhibition attenuates microvascular dysfunction in postischemic skeletal muscle","volume":"271","author":"DL Carden","year":"1996","journal-title":"Am J Physiol"},{"key":"pone.0274427.ref056","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1152\/jappl.1993.75.6.2529","article-title":"Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P-selectin","volume":"75","author":"DL Carden","year":"1993","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0274427.ref057","first-page":"H385","article-title":"Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins","volume":"275","author":"D Carden","year":"1998","journal-title":"Am J Physiol"},{"key":"pone.0274427.ref058","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJM198902093200606","article-title":"Tissue destruction by neutrophils","volume":"320","author":"SJ Weiss","year":"1989","journal-title":"N Engl J Med"},{"key":"pone.0274427.ref059","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1172\/JCI111332","article-title":"Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites","volume":"73","author":"SJ Weiss","year":"1984","journal-title":"J Clin Invest"},{"key":"pone.0274427.ref060","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.4049\/jimmunol.175.5.3329","article-title":"Inhibition of neutrophil elastase by alpha1-protease inhibitor at the surface of human polymorphonuclear neutrophils","volume":"175","author":"B Korkmaz","year":"2005","journal-title":"J Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0274427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T16:57:30Z","timestamp":1662742650000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0274427"}},"subtitle":[],"editor":[{"given":"Pavel","family":"Strnad","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":60,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0274427","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.07.07.499204","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}