Background--Platelet-leukocyte interaction is an early important event for thrombogenesis, and this process is mainly mediated by P-selectin on platelets. Although -tocopherol has been shown to inhibit thrombotic disorders, the effect of -tocopherol on platelet P-selectin expression and platelet-leukocyte interaction is little known.

Methods and Results--We examined whether -tocopherol inhibited human platelet P-selectin expression and platelet-leukocyte interaction. -Tocopherol (50 to 500 µg/mL) inhibited thrombin-induced or phorbol 12-myristate 13-acetate (PMA)-induced P-selectin expression on platelets. -Tocopherol suppressed platelet-mononuclear cell (MNC) interaction, platelet aggregation, and platelet protein kinase C (PKC) activity stimulated with either PMA (100 nmol/L) or thrombin. Inhibitory actions of -tocopherol against the platelet functions were mimicked by staurosporine, a selective PKC inhibitor. After oral supplementation of -tocopherol (300 mg/d for 3 weeks) in healthy subjects, thrombin-mediated or PMA-mediated P-selectin expression, platelet-MNC interaction, and platelet aggregation ex vivo were suppressed.

Conclusions---Tocopherol inhibited P-selectin expression on human platelets and thereby attenuated platelet-MNC interactions, which were mediated at least in part by the inhibition of intraplatelet PKC activity. These actions of -tocopherol on platelet functions provide new insights into the antithromboatherogenic properties of -tocopherol.