Antiphosphatidylserine antibody removes annexin-V and facilitates the binding of prothrombin at the surface of a choriocarcinoma model of trophoblast differentiation.
OBJECTIVE
Trophoblast differentiation is associated with externalization of phosphatidylserine from the inner to the outer surface of the plasma membrane. In this study we tested the hypothesis that concurrent externalization and binding of annexin-V blocks the phosphatidylserine-rich surface from acting as a site for activation of coagulation and that antiphospholipid antibodies lead to a procoagulant state by preventing annexin-V binding.


METHODS
A choriocarcinoma model of trophoblast differentiation, forskolin-activated BeWo cells and immunoperoxidase techniques were used to determine surface and cytoplasmic localization of annexin-V related to differentiation. Monoclonal immunoglobulin M antibodies against phosphatidylserine- and cardiolipin-dependent antigens were used to determine the effects of antiphospholipid antibodies on annexin-V localization and on the binding of prothrombin to the BeWo surface.


RESULTS
During differentiation BeWo cells externalized phosphatidylserine and increased the expression of surface annexin-V. Monoclonal antibody against phosphatidylserine removed annexin-V from the BeWo surface and increased binding of prothrombin.


CONCLUSIONS
Antiphosphatidylserine antibody induces sites for prothrombin binding on the surface of a BeWo model of trophoblast, most likely by removing annexin-V. This mechanism could explain the frequent observation of increased thrombosis at the maternal-fetal interface in miscarriages associated with antiphospholipid antibodies.
Vogt
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Department of Microbiology and Immunology, Wright State University School of Medicine, Dayton, OH 45435, USA.
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D017304:Annexin A5 / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002822:Choriocarcinoma; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007075:Immunoglobulin M / Q000494:pharmacology; D010718:Phosphatidylserines / Q000276:immunology* / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D010718:Phosphatidylserines; D005576:Colforsin; D011516:Prothrombin