Please note that eDoc will be permanently shut down in the first quarter of 2021!      Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Quick Search
My eDoc
Session History
Support Wiki
Direct access to
document ID:

          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)
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.