Up-regulation of the endothelial cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) by autoantibodies in autoimmune vasculitis.
Autoimmune vasculitis is characterized by the presence of autoantibodies, particularly anti-neutrophil cytoplasmic antibodies (ANCA) and anti-nuclear antibodies (ANA), in patient sera. These autoantibodies have an incompletely understood role in development of vascular injury. The expression or up-regulation of cell adhesion molecules is an early phase in the development of an inflammatory vascular lesion. Autoantibody-positive sera from patients with vasculitis were assessed for their ability to modulate adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). Autoantibody-positive serum samples from 11 out of 21 patients with primary vasculitis produced substantial up-regulation of ICAM-1 on HUVEC. Autoantibody-negative samples did not produce adhesion molecule up-regulation. Up-regulation of adhesion molecules on HUVEC was observed with samples positive for ANA, a phenomenon not previously reported. Preincubation of the sera with purified antigens recognized by ANCA failed to block this activation. In addition, MoAbs to ANCA antigens were ineffective at inducing ICAM-1 up-regulation, suggesting that activation is independent of the molecular specificity of the antibody. This capacity of ANCA- and ANA-positive sera to up-regulate adhesion molecules on endothelial cells may be a factor in the vessel wall inflammation seen in ANCA-associated vasculitis.
Johnson
P A
PA
Department of Immunology, Belfast City Hospital, UK.
Alexander
H D
HD
McMillan
S A
SA
Maxwell
A P
AP
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000494:pharmacology; D000974:Antibodies, Antinuclear / Q000494:pharmacology; D001323:Autoantibodies / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects*; D015203:Reproducibility of Results; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1