Anti-beta 2 glycoprotein I antibodies prevent the de-activation of platelets and sustain their phagocytic clearance

Exposure to phosphatidylserine (PS) tags dying and senescent cells for remo val and identifies activated platelets. In this study we followed the fate of PS-exposing platelets in the presence of antibodies purified from System ic Lupus Erythematosus (SLE) and primary Anti-phospholipid Syndrome (APS) p atients' sera by beta 2GPI affinity chromatography. Thrombin-activated plat elets exposed PS and associated to beta 2GPI. Both events were required for recognition by antibodies. Human monocyte-derived macrophages phagocytosed activated platelets only. Each macrophage internalized an average of 3.16 +/- 0.2 platelets after 60min at 37 degreesC. Phagocytosis did not increase after longer incubations (4.65 +/- 0.26 platelets internalized by each mac rophage after 300 min). Recognition of platelets by anti-beta 2GPI antibodi es significantly increased phagocytosis (P < 0.01). Upon withdrawal of thro mbin, platelets downregulated PS (PS exposure t(1/2): 242 min) and the abil ity to be recognized by macrophages. Purified <beta>2GPI bound to PS-exposi ng platelets (association t(1/2): 250min). Phosphatidyl serine exposure and beta 2GPI association had virtually identical kinetics. Antibody binding p rolonged the exposure of the beta 2GPI/PS complex (t(1/2): >1200 min). The ability to phagocytose opsonized platelets was accordingly sustained (5.3 /- 0.2 opsonized platelets were internalized by each macrophage after 60 mi n and 9.4 +/- 0.3 after 300 min). Anti-beta 2GPI antibodies therefore poise activated platelets in a PS-exposing status, preventing the recycling of t heir function and favoring their phagocytic clearance. (C) 2000 Academic Pr ess.