In vitro interactions of c-ANCA (antibodies to proteinase 3) with human endothelial cells.
Several concepts concerning the pathogenicity of antineutrophil cytoplasmic antibodies (ANCA) exist, but till now only sparse data about ANCA-endothelial interactions are available. In this study we have investigated the expression of proteinase 3 (PR-3) in human umbilical endothelial cells (HEC) using purified anti-PR-3 antibodies (C-ANCA) of patients with Wegener's granulomatosis (WG) and monoclonal antibodies to PR-3 (human and murine) as probes. Performing cyto-ELISAs, laser scanning microscopy and Western blot we were able to show that treatment of HEC with IL-1-alpha led to an increased PR-3 expression in the cytoplasm and to a transient translocation into the EC-membrane. Representing an important missing link of ANCA-endothelial interactions, our data give a hint at a possible direct pathogenicity of anti-PR-3 antibodies in WG and other vasculitides.
Mayet
W J
WJ
I. Medizinische Klinik, Universität Mainz, Germany.
Hermann
E M
EM
Csernok
E
E
Gross
W L
WL
Meyer zum Büschenfelde
K H
KH
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D053146:Myeloblastin; D012697:Serine Endopeptidases / Q000032:analysis / Q000276:immunology*; D014470:Umbilical Cord
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D007375:Interleukin-1; D012697:Serine Endopeptidases; D053146:Myeloblastin