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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 474516.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
c-ANCA induce neutrophil-mediated lung injury -a model of acute Wegener's Granulomatosis
Authors:Hattar, K.; Oppermann, S.; Ankele, C.; Weissmann, N.; Schermuly, R. T.; Bohle, R. M.; Moritz, R.; Krogel, B.; Seeger, W.; Grimminger, F.; Sibelius, U.; Grandel, U.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Eur Respir J
Audience:Not Specified
Abstract / Description: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).In this study, a model of ALI in WG was developed using isolated rat lungs. Isolated human polymorphonuclear leukocytes (PMN) were primed with tumour necrosis factor (TNF) to induce surface expression of PR3. Co-perfusion of TNF-primed neutrophils and monoclonal anti-PR3-antibodies (anti-PR3) induced a massive weight gain in isolated lungs. This effect was not observed when control-IgG (IgGc) was co-perfused with TNF-primed PMN. The 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, ANCA-induced lung oedema could be prevented. Inhibition of neutrophil elastase was equally effective in preventing ANCA-induced lung injury.In conclusion, anti-PR3-antibodies induce 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 to develop therapeutic strategies for the treatment of lung injury in fulminant WG.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:University of Giessen Lung Center (UGLC), Giessen, Germany.
Identifiers:ISSN:1399-3003 (Electronic) 0903-1936 (Linking)
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