{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:09:56Z","timestamp":1791331796146,"version":"4.3.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,6,22]],"date-time":"2015-06-22T00:00:00Z","timestamp":1434931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Chinese 973 project","award":["2012CB517702"],"award-info":[{"award-number":["2012CB517702"]}]},{"name":"National Natural Science Fund","award":["81425008"],"award-info":[{"award-number":["81425008"]}]},{"name":"National Natural Science Fund","award":["81370829"],"award-info":[{"award-number":["81370829"]}]},{"name":"National Natural Science Fund","award":["81321064"],"award-info":[{"award-number":["81321064"]}]},{"name":"\u2018National Key Technology Research and Development (R&D) Program\u2019 of the Ministry of Science and Technology of China","award":["2011BAI10B04"],"award-info":[{"award-number":["2011BAI10B04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg-EGTA)-treated human serum. After incubation of serum with supernatants enriched in ANCA-induced NETs, levels of complement components in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b-9 on NETs incubated with heat-inactivated normal human serum (Hi-NHS) or EGTA-treated Hi-NHS (Mg-EGTA-Hi-NHS) were significantly less than that on NETs incubated with NHS or EGTA-treated NHS (Mg-EGTA-NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b-9 concentration decreased from 800\u00b742 \u00b1 244\u00b781 ng\/ml, 7\u00b768 \u00b1 1\u00b750 ng\/ml, 382\u00b715 \u00b1 159\u00b775 ng\/ml in the supernatants enriched in ANCA induced NETs to 479\u00b707 \u00b1 156\u00b72 ng\/ml, 4\u00b786 \u00b1 1\u00b726 ng\/ml, 212\u00b765 \u00b1 44\u00b740 ng\/ml in the supernatants of DNase I-degraded NETs (P &amp;lt; 0\u00b7001, P = 0\u00b7008, P &amp;lt; 0\u00b7001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV.<\/jats:p>","DOI":"10.1111\/cei.12654","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T23:32:47Z","timestamp":1431387167000},"page":"518-527","source":"Crossref","is-referenced-by-count":178,"title":["Neutrophil extracellular traps can activate alternative complement pathways"],"prefix":"10.1093","volume":"181","author":[{"given":"H","family":"Wang","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M-H","family":"Zhao","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,6,22]]},"reference":[{"key":"2021122010160063200_cei12654-bib-0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 revised International Chapel Hill consensus conference nomenclature of vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum"},{"key":"2021122010160063200_cei12654-bib-0002","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/MD.0b013e31817c744b","article-title":"Antineutrophil cytoplasmic autoantibody-associated vasculitis in older patients","volume":"87","author":"Chen","year":"2008","journal-title":"Medicine (Baltimore)"},{"key":"2021122010160063200_cei12654-bib-0003","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1073\/pnas.87.11.4115","article-title":"Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro","volume":"87","author":"Falk","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122010160063200_cei12654-bib-0004","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nm.1959","article-title":"Netting neutrophils in autoimmune small-vessel vasculitis","volume":"15","author":"Kessenbrock","year":"2009","journal-title":"Nat Med"},{"key":"2021122010160063200_cei12654-bib-0005","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature06116","article-title":"Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide","volume":"449","author":"Lande","year":"2007","journal-title":"Nature"},{"key":"2021122010160063200_cei12654-bib-0006","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1182\/blood-2012-03-416156","article-title":"Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity","volume":"120","author":"Sangaletti","year":"2012","journal-title":"Blood"},{"key":"2021122010160063200_cei12654-bib-0007","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s10875-009-9344-2","article-title":"Differential deposition of C4d and MBL in glomeruli of patients with ANCA-negative pauci-immune crescentic glomerulonephritis","volume":"30","author":"Xing","year":"2010","journal-title":"J Clin Immunol"},{"key":"2021122010160063200_cei12654-bib-0008","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2353\/ajpath.2007.060573","article-title":"Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies","volume":"170","author":"Xiao","year":"2007","journal-title":"Am J Pathol"},{"key":"2021122010160063200_cei12654-bib-0009","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/ki.2012.313","article-title":"Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis","volume":"83","author":"Gou","year":"2013","journal-title":"Kidney Int"},{"key":"2021122010160063200_cei12654-bib-0010","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s10875-008-9268-2","article-title":"Complement activation is involved in renal damage in human antineutrophil cytoplasmic autoantibody associated pauci-immune vasculitis","volume":"29","author":"Xing","year":"2009","journal-title":"J Clin Immunol"},{"key":"2021122010160063200_cei12654-bib-0011","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/sj.ki.5002103","article-title":"Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice","volume":"71","author":"Huugen","year":"2007","journal-title":"Kidney Int"},{"key":"2021122010160063200_cei12654-bib-0012","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.4049\/jimmunol.1102404","article-title":"Neutrophil extracellular traps that are not degraded in systemic lupus erythematosus activate complement exacerbating the disease","volume":"188","author":"Leffler","year":"2012","journal-title":"J Immunol"},{"key":"2021122010160063200_cei12654-bib-0013","doi-asserted-by":"crossref","first-page":"J276","DOI":"10.1016\/j.jaut.2009.11.014","article-title":"The complement system in systemic autoimmune disease","volume":"34","author":"Chen","year":"2010","journal-title":"J Autoimmun"},{"key":"2021122010160063200_cei12654-bib-0014","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1440-1797.2009.01086.x","article-title":"Review article: pathogenic role of complement activation in anti-neutrophil cytoplasmic auto-antibody-associated vasculitis","volume":"14","author":"Van Timmeren","year":"2009","journal-title":"Nephrology (Carlton)"},{"key":"2021122010160063200_cei12654-bib-0015","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/ki.2009.420","article-title":"Phosphoinositol 3-kinase-gamma mediates antineutrophil cytoplasmic autoantibody-induced glomerulonephritis","volume":"77","author":"Schreiber","year":"2010","journal-title":"Kidney Int"},{"key":"2021122010160063200_cei12654-bib-0016","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1046\/j.1523-1755.2003.00718.x","article-title":"Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA","volume":"63","author":"Choi","year":"2003","journal-title":"Kidney Int"},{"key":"2021122010160063200_cei12654-bib-0017","doi-asserted-by":"crossref","first-page":"898","DOI":"10.4049\/jimmunol.169.2.898","article-title":"Inhibition of the spontaneous apoptosis of neutrophil granulocytes by the intracellular parasite Leishmania major","volume":"169","author":"Aga","year":"2002","journal-title":"J Immunol"},{"key":"2021122010160063200_cei12654-bib-0018","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.ymthe.2004.08.015","article-title":"Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-ad antibodies","volume":"10","author":"Jiang","year":"2004","journal-title":"Mol Ther"},{"key":"2021122010160063200_cei12654-bib-0019","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1050-4648(03)00057-3","article-title":"A complement C3 fragment equivalent to mammalian C3d from the common carp (Cyprinus carpio): generation in serum after activation of the alternative pathway and detection of its receptor on the lymphocyte surface","volume":"16","author":"Nakao","year":"2004","journal-title":"Fish Shellfish Immunol"},{"key":"2021122010160063200_cei12654-bib-0020","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1002\/art.34619","article-title":"Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis","volume":"64","author":"Nakazawa","year":"2012","journal-title":"Arthritis Rheum"},{"key":"2021122010160063200_cei12654-bib-0021","doi-asserted-by":"crossref","first-page":"e32366","DOI":"10.1371\/journal.pone.0032366","article-title":"Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones","volume":"7","author":"Saffarzadeh","year":"2012","journal-title":"PLOS ONE"},{"key":"2021122010160063200_cei12654-bib-0022","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1016\/j.molimm.2011.06.215","article-title":"In vitro C3 deposition on Cryptococcus capsule occurs via multiple complement activation pathways","volume":"48","author":"Mershon-Shier","year":"2011","journal-title":"Mol Immunol"},{"key":"2021122010160063200_cei12654-bib-0023","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1034\/j.1600-065X.2001.1800103.x","article-title":"Structure and biology of complement protein C3, a connecting link between innate and acquired immunity","volume":"180","author":"Sahu","year":"2001","journal-title":"Immunol Rev"},{"key":"2021122010160063200_cei12654-bib-0024","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1681\/ASN.2013060606","article-title":"Enhanced formation and disordered regulation of NETs in myeloperoxidase-ANCA-associated microscopic polyangiitis","volume":"25","author":"Nakazawa","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"2021122010160063200_cei12654-bib-0025","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1002\/art.34619","article-title":"Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis","volume":"64","author":"Nakazawa","year":"2012","journal-title":"Arthritis Rheum"},{"key":"2021122010160063200_cei12654-bib-0026","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1182\/blood-2010-05-283564","article-title":"Complement alternative pathway acts as a positive feedback amplification of neutrophil activation","volume":"117","author":"Camous","year":"2011","journal-title":"Blood"},{"key":"2021122010160063200_cei12654-bib-0027","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.4049\/jimmunol.158.9.4444","article-title":"Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils","volume":"158","author":"Wirthmueller","year":"1997","journal-title":"J Immunol"},{"key":"2021122010160063200_cei12654-bib-0028","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1681\/ASN.2008050497","article-title":"C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis","volume":"20","author":"Schreiber","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2021122010160063200_cei12654-bib-0029","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/S0002-9440(10)64461-6","article-title":"Generation of C5a by phagocytic cells","volume":"161","author":"Huber-Lang","year":"2002","journal-title":"Am J Pathol"},{"key":"2021122010160063200_cei12654-bib-0030","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1093\/ndt\/gfn586","article-title":"Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis","volume":"24","author":"Chen","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"2021122010160063200_cei12654-bib-0031","doi-asserted-by":"crossref","first-page":"e38317","DOI":"10.1371\/journal.pone.0038317","article-title":"p38MAPK, ERK and PI3K signaling pathways are involved in C5a-primed neutrophils for ANCA-mediated activation","volume":"7","author":"Hao","year":"2012","journal-title":"PLOS ONE"},{"key":"2021122010160063200_cei12654-bib-0032","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1136\/annrheumdis-2013-203430","article-title":"Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease","volume":"73","author":"Kambas","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"2021122010160063200_cei12654-bib-0033","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the absence of C3: a new complement activation pathway","volume":"12","author":"Huber-Lang","year":"2006","journal-title":"Nat Med"},{"key":"2021122010160063200_cei12654-bib-0034","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1182\/blood-2012-02-412080","article-title":"Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway","volume":"120","author":"Krisinger","year":"2012","journal-title":"Blood"},{"key":"2021122010160063200_cei12654-bib-0035","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1159\/000356980","article-title":"Myeloperoxidase directs properdin-mediated complement activation","volume":"6","author":"O'Flynn","year":"2014","journal-title":"J Innate Immun"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12654","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/181\/3\/518\/41791004\/cei12654.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/181\/3\/518\/41791004\/cei12654.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T07:50:24Z","timestamp":1691653824000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/181\/3\/518\/6422077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,22]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,6,22]]},"published-print":{"date-parts":[[2015,8,13]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12654","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725501959.793548108","asserted-by":"object"}]},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,9]]},"published":{"date-parts":[[2015,6,22]]}}}