Pierangeli Silvia S, Vega-Ostertag Mariano, Liu Xiaowei, Girardi Guillermina
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA.
Ann N Y Acad Sci. 2005 Jun;1051:413-20. doi: 10.1196/annals.1361.083.
Antiphospholipid antibodies (aPLs) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPL-induced thrombosis is incompletely understood, but it is thought to involve platelet and endothelial cell activation as well as pro-coagulant effects of aPL antibody directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-antibody treated mice. We hypothesized that aPL antibodies activate complement, generating split products that induce thrombosis. To test this hypothesis, we used an in vivo model of thrombosis in which aPL antibodies induce a significant increase in thrombus size and a mouse model of endothelial cell activation in which aPLs induce significant adhesion of leukocytes (WBCs) to endothelial cells. We found that mice deficient in complement components C3 and C5 were resistant to enhanced thrombosis and endothelial cell activation induced by aPL antibodies. Furthermore, inhibition of C5 activation using anti-C5 mAb prevented thrombophilia induced by aPL antibodies. Our data show that complement activation mediates two important effectors of aPL antibodies: induction of thrombosis and endothelial activation.
抗磷脂抗体（aPLs）已被证明可诱发血栓形成、激活内皮细胞并导致胎儿丢失。aPL诱发血栓形成的发病机制尚未完全明确，但据认为其涉及血小板和内皮细胞的激活，以及aPL抗体对凝血途径成分的促凝作用。最近的研究表明，补体的失控激活会导致经aPL抗体处理的小鼠出现胎儿死亡。我们推测aPL抗体激活补体，产生诱导血栓形成的裂解产物。为了验证这一假设，我们使用了一个血栓形成的体内模型，其中aPL抗体可使血栓大小显著增加；还使用了一个内皮细胞激活的小鼠模型，其中aPLs可诱导白细胞（WBCs）与内皮细胞的显著黏附。我们发现，缺乏补体成分C3和C5的小鼠对aPL抗体诱导的血栓形成增强和内皮细胞激活具有抗性。此外，使用抗C5单克隆抗体抑制C5激活可预防aPL抗体诱导的血栓形成倾向。我们的数据表明，补体激活介导了aPL抗体的两个重要效应：血栓形成的诱导和内皮激活。
