{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:58:39Z","timestamp":1761807519846,"version":"3.37.3"},"reference-count":37,"publisher":"European Respiratory Society (ERS)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2009,12,9]]},"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:p>Anti-neutrophil cytoplasmic antibodies (c-ANCA) targeting proteinase 3 (PR3) are implicated in the pathogenesis of Wegener's granulomatosis (WG). Fulminant disease can present as acute lung injury (ALI).<\/jats:p><jats:p>In this study, a model of ALI in WG was developed using isolated rat lungs. Isolated human polymorphonuclear leukocytes (PMNs) were primed with tumour necrosis factor (TNF) to induce surface expression of PR3.<\/jats:p><jats:p>Co-perfusion of TNF-primed neutrophils and monoclonal anti-PR3 antibodies induced a massive weight gain in isolated lungs. This effect was not observed when control immunoglobulin G was co-perfused with TNF-primed PMNs. The c-ANCA-induced oedema formation was paralleled by an increase in the capillary filtration coefficient as a marker of increased pulmonary endothelial permeability. In contrast, pulmonary artery pressure was not affected. In the presence of the oxygen radical scavenger superoxide dismutase and a NADPH oxidase inhibitor, c-ANCA-induced lung oedema could be prevented. Inhibition of neutrophil elastase was equally effective in preventing c-ANCA-induced lung injury.<\/jats:p><jats:p>In conclusion, anti-PR3 antibodies induced neutrophil mediated, elastase- and oxygen radical-dependent ALI in the isolated lung. This experimental model supports the hypothesis of a pathogenic role for c-ANCA in WG and offers the possibility of the development of therapeutic strategies for the treatment of lung injury in fulminant WG.<\/jats:p>","DOI":"10.1183\/09031936.00143308","type":"journal-article","created":{"date-parts":[[2009,12,24]],"date-time":"2009-12-24T02:12:29Z","timestamp":1261620749000},"page":"187-195","source":"Crossref","is-referenced-by-count":24,"title":["c-ANCA-induced neutrophil-mediated lung injury: a model of acute Wegener's granulomatosis"],"prefix":"10.1183","volume":"36","author":[{"given":"K.","family":"Hattar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Oppermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Ankele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Weissmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.T.","family":"Schermuly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.M.","family":"Bohle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Moritz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Kr\u00f6gel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Seeger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Grimminger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Sibelius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Grandel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2009,12,23]]},"reference":[{"key":"2024102020095955000_36.1.187.1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1179\/acb.2007.016","article-title":"Pulmonary renal syndromes","volume":"62","author":"Brusselle","year":"2007","journal-title":"Acta Clin Belg"},{"key":"2024102020095955000_36.1.187.2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200101000-00003"},{"key":"2024102020095955000_36.1.187.3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/ajcp\/104.1.7","article-title":"The pathologic spectrum of pulmonary lesions in patients with anti-neutrophil cytoplasmic autoantibodies specific for anti-proteinase 3 and anti-myeloperoxidase","volume":"104","author":"Gaudin","year":"1995","journal-title":"Am J Clin Pathol"},{"key":"2024102020095955000_36.1.187.4","doi-asserted-by":"publisher","DOI":"10.1186\/cc2881"},{"key":"2024102020095955000_36.1.187.5","first-page":"L1083","article-title":"Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide","volume":"279","author":"Chignard","year":"2000","journal-title":"Am J Physiol"},{"key":"2024102020095955000_36.1.187.6","doi-asserted-by":"publisher","DOI":"10.1097\/01.moh.0000190113.31027.d5"},{"key":"2024102020095955000_36.1.187.7","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-948288"},{"key":"2024102020095955000_36.1.187.8","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1164\/ajrccm\/143.2.401","article-title":"Bronchoalveolar lavage analysis in Wegener's granulomatosis. 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