Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

Abstract

Objective. To investigate the ability of human anti-&-glycoprotein I (anti-&GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.Methods. Six human affinity-purified polyclonal anti-P,GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent f3,GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F,, (6-keto-PGF1,) secretion.Results. The affinity-purified IgG and the MAb with anti-&GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human P,GPI. After EC binding, both polycJonaJ and monoclonal antibodies up-regulated adhesion molecule expres-

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

“…Several studies have demonstrated that aPL activate ECs in vitro, suggesting a mechanism by which these antibodies exert procoagulant properties (15,49,50). Utilizing a mouse model, our group has previously demonstrated that aPL antibodies increase leukocyte adhesion to ECs of cremasteric muscle postcapillary venules, suggesting that these antibodies induce activation of ECs in vivo and that these effects correlate with enhanced thrombus formation (37).…”

Specificities, properties, and clinical significance of antiprothrombin antibodies

“…Some aPL bind to endothelial cells, suggesting that aPL may interact with endothelial cells and thus promote thrombosis (68,69). APTs can bind to immobilized PS in the presence of calcium and prothrombin (28,29), and a LAC IgG preparation can enhance the binding of prothrombin to endothelial cells and increase thrombin generation on these cells (45), suggesting that APT may concentrate prothrombin on cell surface phospholipids and thus lead to a hypercoagulable state.…”

How do antiphospholipid antibodies bind β2‐glycoprotein I?

“…44). ␤ 2 GPIdependent aPL may cause atherosclerosis by direct activation of the vascular endothelium (40,45,46), increased clearance of oxidized LDL (36), or reduced paraoxonase activity, leading to increased oxidation of LDL (47).…”