Journalartikel

Jahr der Veröffentlichung: 2010

Seiten: 187-195

Zeitschrift: European Respiratory Journal

Bandnummer: 36

Heftnummer: 1

ISSN: 0903-1936

eISSN: 1399-3003

Open Access Status: Bronze

DOI Link: https://doi.org/10.1183/09031936.00143308

Verlag: European Respiratory Society

Abstract: 

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 (PMNs) were primed with tumour necrosis factor (TNF) to induce surface expression of PR3.

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.

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.

Harvard-Zitierstil: Hattar, K., Oppermann, S., Ankele, C., Weissmann, N., Schermuly, R., Bohle, R., et al. (2010) c-ANCA-induced neutrophil-mediated lung injury: a model of acute Wegener's granulomatosis, European Respiratory Journal, 36(1), pp. 187-195. https://doi.org/10.1183/09031936.00143308

APA-Zitierstil: Hattar, K., Oppermann, S., Ankele, C., Weissmann, N., Schermuly, R., Bohle, R., Moritz, R., Kroegel, B., Seeger, W., Grimminger, F., Sibelius, U., & Grandel, U. (2010). c-ANCA-induced neutrophil-mediated lung injury: a model of acute Wegener's granulomatosis. European Respiratory Journal. 36(1), 187-195. https://doi.org/10.1183/09031936.00143308