title: Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis.
abstract: Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe vasculitis in different organs (e.g. kidney, nose and lung). Little is known about the expression and distribution of PR-3 in the lung. We found that PR-3 is expressed in normal lung tissue and is upregulated in lung tissue of patients with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and macrophages, and not the neutrophils, express PR-3 most strongly and may contribute to lung damage in patients with WG via direct interaction with antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR-3 expression in parenchymal cells of lung tissue could be at least one missing link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.
authors: Department of Medicine, University of Mainz, Germany.
authors: Holger
authors: H
authors: Brockmann
authors: Andreas
authors: A
authors: Schwarting
authors: Jörg
authors: J
authors: Kriegsmann
authors: Peter
authors: P
authors: Petrow
authors: Andreas
authors: A
authors: Gaumann
authors: Klaus-Michael
authors: KM
authors: Müller
authors: Peter Robert
authors: PR
authors: Galle
authors: Werner
authors: W
authors: Mayet
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014890:Granulomatosis with Polyangiitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008168:Lung / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D053146:Myeloblastin; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D053146:Myeloblastin