{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:55Z","timestamp":1790742055052,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["MOST 109-2314-B040-021"],"award-info":[{"award-number":["MOST 109-2314-B040-021"]}]},{"name":"National Science and Technology Council","award":["NSTC 112-2314-B040-015"],"award-info":[{"award-number":["NSTC 112-2314-B040-015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.<\/jats:p>","DOI":"10.3390\/ijms25189917","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T01:52:31Z","timestamp":1726624351000},"page":"9917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0140-9943","authenticated-orcid":false,"given":"Bor-Show","family":"Tzang","sequence":"first","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Yang","family":"Chin","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chen","family":"Tzang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Taiwan University, Taipei City 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hua","family":"Chuang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-1423","authenticated-orcid":false,"given":"Der-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"College of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Rheumatology and Immunology Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Ching","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/joim.13022","article-title":"The antiphospholipid syndrome\u2014Often overlooked cause of vascular occlusions?","volume":"287","author":"Svenungsson","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1002\/art.40901","article-title":"The Epidemiology of Antiphospholipid Syndrome: A Population-Based Study","volume":"71","author":"Pham","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12959-022-00409-8","article-title":"The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: A 14-year nationwide population-based study","volume":"20","author":"Yao","year":"2022","journal-title":"Thromb. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrrheum.2016.24","article-title":"Connective tissue diseases: Mitochondria drive NETosis and inflammation in SLE","volume":"12","author":"Boilard","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Corsiero, E., Pratesi, F., Prediletto, E., Bombardieri, M., and Migliorini, P. (2016). NETosis as Source of Autoantigens in Rheumatoid Arthritis. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00485"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"S\u00f6derberg, D., and Segelmark, M. (2016). Neutrophil Extracellular Traps in ANCA-Associated Vasculitis. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00256"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wirestam, L., Arve, S., Linge, P., and Bengtsson, A.A. (2019). Neutrophils-Important Communicators in Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02734"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.trsl.2020.04.006","article-title":"Antiphospholipid syndrome","volume":"225","author":"Petri","year":"2020","journal-title":"Transl. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1038\/s41467-019-09801-x","article-title":"Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome","volume":"10","author":"Ali","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/art.39938","article-title":"In Vivo Role of Neutrophil Extracellular Traps in Antiphospholipid Antibody-Mediated Venous Thrombosis","volume":"69","author":"Meng","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1002\/art.41460","article-title":"Anti-Neutrophil Extracellular Trap Antibodies and Impaired Neutrophil Extracellular Trap Degradation in Antiphospholipid Syndrome","volume":"72","author":"Zuo","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1002\/art.39247","article-title":"Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: A newly identified mechanism of thrombosis in the antiphospholipid syndrome","volume":"67","author":"Yalavarthi","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/cbf.3363","article-title":"Anti-\u03b22GPI\/\u03b22GPI induces human neutrophils to generate NETs by relying on ROS","volume":"37","author":"You","year":"2019","journal-title":"Cell Biochem. Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11926-020-00936-1","article-title":"NETs in APS: Current Knowledge and Future Perspectives","volume":"22","author":"Tambralli","year":"2020","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Martirosyan, A., Aminov, R., and Manukyan, G. (2019). Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01609"},{"key":"ref_16","first-page":"2652","article-title":"Targeted delivery of protein arginine deiminase-4 inhibitors to limit arterial intimal NETosis and preserve endothelial integrity","volume":"117","author":"Molinaro","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Xu, Z., and Liu, Z. (2022). Impact of Neutrophil Extracellular Traps on Thrombosis Formation: New Findings and Future Perspective. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.910908"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1128\/CMR.00040-16","article-title":"Human Parvoviruses","volume":"30","author":"Qiu","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ros, C., Bieri, J., and Leisi, R. (2020). The VP1u of Human Parvovirus B19: A Multifunctional Capsid Protein with Biotechnological Applications. Viruses, 12.","DOI":"10.3390\/v12121463"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1128\/CMR.15.3.485-505.2002","article-title":"Human parvovirus B19","volume":"15","author":"Heegaard","year":"2002","journal-title":"Clin Microbiol Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1177\/096120330000900714","article-title":"Parvovirus B19 infection associated with the production of anti-neutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (aCL)","volume":"9","author":"Chou","year":"2000","journal-title":"Lupus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cca.2006.10.016","article-title":"The association of VP1 unique region protein in acute parvovirus B19 infection and antiphospholipid antibody production","volume":"378","author":"Tzang","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1080\/21505594.2017.1385691","article-title":"Antigenicity analysis of human parvovirus B19-VP1u protein in the induction of anti-phospholipid syndrome","volume":"9","author":"Lin","year":"2018","journal-title":"Virulence"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.cca.2010.04.004","article-title":"The association of anti-parvovirus B19-VP1 unique region antibodies with antiphospholipid antibodies in patients with antiphospholipid syndrome","volume":"411","author":"Chen","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cca.2008.05.012","article-title":"Up-regulation of adhesion molecule expression and induction of TNF-alpha on vascular endothelial cells by antibody against human parvovirus B19 VP1 unique region protein","volume":"395","author":"Tzang","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_26","first-page":"1320","article-title":"Effects of antibodies against human parvovirus B19 on angiogenic signaling","volume":"21","author":"Su","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"759","DOI":"10.3892\/mmr.2021.12399","article-title":"Effect of N-terminal region of human parvovirus B19-VP1 unique region on cardiac injury in na\u00efve mice","volume":"24","author":"Hung","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cca.2007.03.014","article-title":"Induction of antiphospholipid antibodies and antiphospholipid syndrome-like autoimmunity in naive mice with antibody against human Parvovirus B19 VP1 unique region protein","volume":"382","author":"Tzang","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_29","first-page":"56697","article-title":"Stenosis of the Inferior Vena Cava: A Murine Model of Deep Vein Thrombosis","volume":"130","author":"Payne","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1177\/0961203316640912","article-title":"Systematic review of case reports of antiphospholipid syndrome following infection","volume":"25","year":"2016","journal-title":"Lupus."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/13550280490261752","article-title":"Middle cerebral artery thrombosis in course of parvovirus B19 infection in a young adult: A new risk factor for stroke?","volume":"10","author":"Mandrioli","year":"2004","journal-title":"J. Neurovirol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"bcr2015213492","DOI":"10.1136\/bcr-2015-213492","article-title":"Parvovirus leading to thrombotic microangiopathy in a healthy adult","volume":"2016","author":"Prasad","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s12024-020-00263-y","article-title":"Sudden death of a young adult with coronary artery vasculitis, coronary aneurysms, parvovirus B19 infection and Kawasaki disease","volume":"16","author":"Flossdorf","year":"2020","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.hemonc.2018.05.003","article-title":"Parvovirus-induced thrombocytopenia","volume":"12","author":"Yirgin","year":"2019","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_35","first-page":"e30279","article-title":"Immune Thrombocytopenic Purpura and Paradoxical Thrombosis: A Systematic Review of Case Reports","volume":"14","author":"Ali","year":"2022","journal-title":"Cureus"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.thromres.2020.10.005","article-title":"Why thromboembolism occurs in some patients with thrombocytopenia and treatment strategies","volume":"196","author":"Han","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1182\/blood-2013-04-457671","article-title":"NETosis: How vital is it?","volume":"122","author":"Yipp","year":"2013","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1160\/TH17-09-0630","article-title":"The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases","volume":"118","author":"Bonaventura","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_39","first-page":"w14352","article-title":"Neutrophil extracellular traps in health and disease","volume":"146","author":"Hasler","year":"2016","journal-title":"Swiss Med. Wkly."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads toneutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1126\/science.1101400","article-title":"Human PAD4 regulates histone arginine methylation levels via demethylimination","volume":"306","author":"Wang","year":"2004","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1083\/jcb.200806072","article-title":"Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation","volume":"184","author":"Wang","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13076","DOI":"10.1073\/pnas.1200419109","article-title":"Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis","volume":"109","author":"Demers","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8674","DOI":"10.1073\/pnas.1301059110","article-title":"Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice","volume":"110","author":"Martinod","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/jth.13951","article-title":"Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients","volume":"16","author":"Mauracher","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/art.1780400115","article-title":"Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus","volume":"40","author":"Loizou","year":"1997","journal-title":"Arthritis Rheum."},{"key":"ref_47","first-page":"1286","article-title":"Neutrophil extracellular traps: Mechanisms of formation and role in health and disease","volume":"79","author":"Vorobjeva","year":"2014","journal-title":"Biochemistry"},{"key":"ref_48","first-page":"1178","article-title":"NETosis: Molecular Mechanisms, Role in Physiology and Pathology","volume":"85","author":"Vorobjeva","year":"2020","journal-title":"Biochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.coi.2019.05.004","article-title":"Cell intrinsic functions of neutrophils and their manipulation by pathogens","volume":"60","author":"Allen","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.it.2019.01.006","article-title":"Neutrophil degranulation, plasticity, and cancer metastasis","volume":"40","author":"Mollinedo","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e92926","DOI":"10.1172\/jci.insight.92926","article-title":"Lupus and proliferative nephritis are PAD4 independent in murine models","volume":"2","author":"Gordon","year":"2017","journal-title":"JCI Insight"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lloyd, K.A., Wigerblad, G., Sahlstr\u00f6m, P., Garimella, M.G., Chemin, K., Steen, J., Titcombe, P.J., Marklein, B., Zhou, D., and St\u00e5lesen, R. (2019). Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03033"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Arvia, R., Stincarelli, M.A., Manaresi, E., Gallinella, G., and Zakrzewska, K. (2024). Parvovirus B19 in Rheumatic Diseases. Microorganisms, 12.","DOI":"10.3390\/microorganisms12081708"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Vel\u00e1squez, M., Pel\u00e1ez, L.F., Rojas, M., Narv\u00e1ez-S\u00e1nchez, R., Vel\u00e1squez, J.A., Escudero, C., San Mart\u00edn, S., and Cadavid, \u00c1.P. (2021). Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.764702"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00281-022-00916-w","article-title":"Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome","volume":"44","author":"Knight","year":"2022","journal-title":"Semin Immunopathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.1161\/01.CIR.96.12.4380","article-title":"Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice","volume":"96","author":"Edwards","year":"1997","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1002\/art.21157","article-title":"Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia","volume":"52","author":"Pierangeli","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.blre.2009.07.002","article-title":"Basic mechanisms and pathogenesis of venous thrombosis","volume":"23","author":"Esmon","year":"2009","journal-title":"Blood Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s42255-022-00591-z","article-title":"Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo","volume":"4","author":"Murphy","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3892\/etm.2021.9784","article-title":"Differentiation of HL-60 cells in serum-free hematopoietic cell media enhances the production of neutrophil extracellular traps","volume":"21","author":"Guo","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Monti, M., Iommelli, F., De Rosa, V., Carriero, M.V., Miceli, R., Camerlingo, R., Di Minno, G., and Del Vecchio, S. (2017). Integrin-dependent cell adhesion to neutrophil extracellular traps through engagement of fibronectin in neutrophil-like cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171362"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tsai, C.C., Tzang, B.S., Chiang, S.Y., Hsu, G.J., and Hsu, T.C. (2009). Increased expression of Matrix Metalloproteinase 9 in liver from NZB\/W F1 mice received antibody against human parvovirus B19 VP1 unique region protein. J. Biomed. Sci., 16.","DOI":"10.1186\/1423-0127-16-14"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wang, H., Wang, Q., Wang, J., Guo, C., Kleiman, K., Meng, H., Knight, J.S., and Eitzman, D.T. (2017). Proprotein convertase subtilisin\/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14307-x"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jss.2018.08.014","article-title":"Citrullinated Histone H3: Early Biomarker of Neutrophil Extracellular Traps in Septic Liver Damage","volume":"234","author":"Nomura","year":"2019","journal-title":"J. Surg. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.jvs.2013.11.007","article-title":"Factors that influence perforator thrombosis and predict healing with perforator sclerotherapy for venous ulceration without axial reflux","volume":"59","author":"Kiguchi","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11239-013-1034-5","article-title":"Novel mediators and biomarkers of thrombosis","volume":"37","author":"Sexton","year":"2014","journal-title":"J. Thromb. Thrombolysis"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:56:02Z","timestamp":1760111762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,13]]},"references-count":66,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25189917"],"URL":"https:\/\/doi.org\/10.3390\/ijms25189917","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,13]]}}}