Inhibition of APC anticoagulant activity on oxidized phospholipid by anti–β2-glycoprotein I monoclonal antibodies

摘要: Activated protein C (APC) anticoagulant activity and the ability to be inhibited by auto-antibodies associated with thrombosis are strongly augmented presence of phosphatidylethanolamine (PE) phospholipid oxidation. β2-glycoprotein I (β2-GPI) is a major antigen for antiphospholipid antibodies present in patients syndrome. We therefore investigated whether anti–β2-GPI monoclonal (mAbs) could inhibit APC similar membrane specificity. Five mouse mAbs that reacted different epitopes on β2-GPI were examined. Each PE-, oxidation–dependent enhancement required antibody divalency. A chimeric retains but relatively unaffected S, PE, or oxidation was not antibodies. In purified systems, mAb inhibition factor Va inactivation greater S β2-GPI. Surprisingly, although did increase affinity membranes, PE had little influence complex vesicles. conclude function specifically contribute hypercoaguable state disrupting specific protein-protein interactions induced PE-containing membranes.