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Human endothelial cells express proteinase 3, the target antigen of
anticytoplasmic antibodies in Wegener's granulomatosis
WJ Mayet, E Csernok, C Szymkowiak, WL Gross and KH Meyer zum Buschenfelde
I. Medical Department of Medicine, University of Mainz, Germany.
Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA),
especially proteinase 3 (PR-3), have proved to be a useful clinical tool
confirming the diagnosis or monitoring disease activity of Wegener's
granulomatosis (WG). Although several concepts concerning the
pathophysiologic potentials of ANCA have been discussed, only sparse data
about ANCA-endothelium interactions have been available. In this study, we
have investigated the expression of PR-3 in cytokine- treated human
endothelial cells using purified anti-PR-3 antibodies of patients with WG,
murine and human monoclonal anti-PR-3 antibodies as probes. We were able to
show that tumor necrosis factor-alpha, interleukin-1 alpha/beta, and
interferon-gamma led to an increased PR-3 expression in the cytoplasm of
endothelial cells by performing polymerase chain reaction analysis, Western
blot, cyto-enzyme-linked immunosorbent assays, and confocal laser scanning
microscopy. Moreover, PR-3 was also translocated into the cell membrane,
becoming accessible to ANCA. Our data suggest a possible direct pathogenic
effect of anti- PR-3 antibodies in WG and other vasculitides. Anti-PR-3
antibodies represent an important missing link in ANCA-endothelial
interactions.
Volume 82,
Issue 4,
pp. 1221-1229,
08/15/1993
Copyright © 1993 by The American Society of Hematology
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