IgG anti-endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner.
OBJECTIVE
To investigate the ability of anti-endothelial cell antibodies (AECA) to modulate endothelial cell function.


METHODS
The effects of purified IgG from 11 patients with systemic lupus erythematosus (SLE) and 4 patients with systemic vasculitis on the expression of adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin) by human umbilical vein endothelial cells and on the adhesion of the human promyelocytic cell line U937 were examined in vitro.


RESULTS
IgG from 6 of 8 AECA-positive SLE patients and 3 of 3 AECA-positive systemic vasculitis patients up-regulated adhesion molecule expression and leukocyte adhesion to endothelial cells. The 4 AECA-negative samples had no effect. Transfer experiments demonstrated that at later time points (2-8 hours) after AECA addition, endothelium-derived interleukin-1 (IL-1) accounted for the ability of AECA to increase leukocyte adhesion. However, even within very short times after addition of AECA (<30 minutes), endothelial cells released a distinct transferable mediator with similar effects.


CONCLUSIONS
AECA in patients with SLE or systemic vasculitis may contribute to pathogenesis by increasing leukocyte adhesion to endothelial cells. AECA act by inducing the release of at least two endothelium-derived mediators, one (as-yet-unidentified) rapidly and another (IL-1) more slowly, both of which stimulate endothelial cells in an autocrine manner.
Carvalho
D
D
King's College, London, UK.
Savage
C O
CO
Isenberg
D
D
Pearson
J D
JD
D019138:Antibodies, Blocking / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D019898:Autocrine Communication / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007962:Leukocytes / Q000166:cytology* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000276:immunology*
D019138:Antibodies, Blocking; D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; C087589:anti-endothelial cell antibody