Bax activators potentiate coated-platelet formation.

Abstract

Activation of platelets with collagen plus thrombin produces a subset of cells known as coated-platelets. Coated-platelets retain several alpha-granule proteins on their surface, express phosphatidylserine (PS), lose mitochondrial potential and release microparticles. A number of these characteristics are also observed in apoptotic cells, and this similarity leads to the hypothesis that mechanisms controlling initiation of apoptosis might also affect generation of coated-platelets. In this report, we demonstrate that BH3 mimetics, molecules that facilitate apoptosis by releasing pro-apoptotic Bax from its antiapoptotic partner Bcl-2, are able to promote coated-platelet formation as monitored by several different markers of these cells. Specifically, gossypol and methoxy-antimycin (MAM) promote fibrinogen retention, mitochondrial depolarization, and PS exposure upon activation with thrombin plus convulxin, a ligand of the glycoprotein VI collagen receptor. Gossypol also potentiates microparticle release by convulxin plus thrombin activated platelets although MAM does not. In addition, Bax activators together with thrombin generate coated-platelets, effectively bypassing the requirement for convulxin. These findings further support a close relationship between apoptotic-like events and the production of coated-platelets.