ANTIPHOSPHATIDYLSERINE ANTIBODY REMOVES ANNEXIN-V AND FACILITATES THEBINDING OF PROTHROMBIN AT THE SURFACE OF A CHORIOCARCINOMA MODEL OF TROPHOBLAST DIFFERENTIATION

OBJECTIVE: Trophoblast differentiation is associated with externalizat ion of phosphatidylserine from the inner to the outer surface of the p lasma membrane. in this study we tested the hypothesis that concurrent externalization and binding of annexin-V blocks the phosphatidylserin e-rich surface from acting as a site for activation of coagulation and that antiphospholipid antibodies lead to a procoagulant state by prev enting annexin-V binding. STUDY DESIGN: A choriocarcinoma model of tro phoblast differentiation, forskolin-activated BeWo cells and immunoper oxidase techniques were used to determine surface and cytoplasmic loca lization of annexin-V related to differentiation. Monoclonal immunoglo bulin M antibodies against phosphatidylserine-and cardiolipin-dependen t antigens were used to determine the effects of antiphospholipid anti bodies on annexin-V localization and on the binding of prothrombin to the BeWo surface. RESULTS: During differentiation BeWo cells externali zed phosphatidylserine and increased the expression of surface annexin -V. Monoclonal antibody against phosphatidylserine removed annexin-V f rom the BeWo surface and increased binding of prothrombin. CONCLUSION: Antiphosphatidylserine antibody induces sites for prothrombin binding on the surface of a BeWo model of trophoblast, most likely by removin g annexin-V. This mechanism could explain the frequent observation of increased thrombosis at the maternal-fetal interface in miscarriages a ssociated with antiphospholipid antibodies.