Cilostazol inhibits platelet-leukocyte interaction by suppression of platelet activation.
The influence of three anti-platelet drugs, cilostazol, aspirin, and tirofiban, was investigated on platelet-leukocyte interaction by flow cytometry. When platelets and leukocytes were pre-incubated with anti-platelet drugs and stimulated by thrombin or collagen, cilostazol was found to inhibit platelet adhesion to monocytes and polymorphonuclear cells (PMNs). Similar effects were observed with anti-CD62P antibody, while aspirin and tirofiban did not appear to interfere with interaction between platelets and leukocytes. In the platelets pre-incubated with anti-platelet drugs, cilostazol significantly reduced CD62P expression and GPIIb/IIIa activation on platelet surface stimulated by thrombin or collagen. Aspirin inhibited CD62P expression and GPIIb/IIIa activation induced by collagen, but not thrombin. Tirofiban significantly blocked GPIIb/IIIa activation induced with both, and weakly inhibited CD62P expression induced by collagen. When added after stimulation of platelets, cilostazol again significantly inhibited CD62P expression and GPIIb/IIIa activation, although to a lesser extent than in the pre-incubation study. Aspirin hardly inhibited CD62P expression or GPIIb/IIIa activation, while tirofiban strongly blocked GPIIb/IIIa activation induced by thrombin or collagen, but had little effects on CD62P expression. In conclusion, our results suggest that cilostazol inhibits platelet-leukocyte interaction by reducing CD62P expression on the platelet surface.
Ito
Hideki
H
Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co, Ltd, Kawauchi-cho, Tokushima, Japan. h_ito@research.otsuka.co.jp
Miyakoda
Goro
G
Mori
Toyoki
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002469:Cell Separation; D000077407:Cilostazol; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019007:P-Selectin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013777:Tetrazoles; D014443:Tyrosine; D003094:Collagen; D000242:Cyclic AMP; D013917:Thrombin; D000077466:Tirofiban; D000077407:Cilostazol; D001241:Aspirin; D002118:Calcium