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


RESULTS
We examined whether alpha-tocopherol inhibited human platelet P-selectin expression and platelet-leukocyte interaction. Alpha-tocopherol (50 to 500 microg/mL) inhibited thrombin-induced or phorbol 12-myristate 13-acetate (PMA)-induced P-selectin expression on platelets. alpha-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 alpha-tocopherol against the platelet functions were mimicked by staurosporine, a selective PKC inhibitor. After oral supplementation of alpha-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
alpha-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 alpha-tocopherol on platelet functions provide new insights into the antithromboatherogenic properties of alpha-tocopherol.
Murohara
Toyoaki
T
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan. murohara@med.nagoya-u.ac.jp
Ikeda
Hisao
H
Otsuka
Yoritaka
Y
Aoki
Mika
M
Haramaki
Nobuya
N
Katoh
Atsushi
A
Takajo
Yoshinori
Y
Imaizumi
Tsutomu
T
D000284:Administration, Oral; D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D011493:Protein Kinase C; D013917:Thrombin; D024502:alpha-Tocopherol; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate