Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia.
OBJECTIVE
Antiphospholipid antibodies (aPL) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPL-induced thrombosis, although not completely understood, may involve platelet and endothelial cell activation as well as procoagulant effects of aPL directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-treated mice. In this study, we tested the hypothesis that aPL are responsible for activation of complement, thus generating split products that induce thrombosis.


METHODS
To study thrombus dynamics and adhesion of leukocytes we used in vivo murine models of thrombosis and microcirculation, in which injections of aPL were used.


RESULTS
Mice deficient in complement components C3 and C5 were resistant to the enhanced thrombosis and endothelial cell activation that was induced by aPL. Furthermore, inhibition of C5 activation using anti-C5 monoclonal antibodies prevented thrombophilia induced by aPL.


CONCLUSIONS
These data show that complement activation mediates 2 important effectors of aPL, induction of thrombosis and activation of endothelial cells.
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. spierangeli@msm.edu
Silvia S
SS
Pierangeli
Guillermina
G
Girardi
Mariano
M
Vega-Ostertag
Xiaowei
X
Liu
Ricardo G
RG
Espinola
Jane
J
Salmon
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000494:pharmacology; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000235:genetics / Q000276:immunology*; D003182:Complement C5 / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019851:Thrombophilia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D017152:Antibodies, Antiphospholipid; D003176:Complement C3; D003182:Complement C5; D007074:Immunoglobulin G