12(S)-HETE plays a role as a mediator of expression of platelet CD62 (P-selectin)

Abstract

The role of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE), an abundant lipoxygenase product from arachidonic acid in platelets, remains unknown. We investigated and characterized the role of 12(S)-HETE in platelet activation. 12(S)-HETE production and CD62 expression were increased by stimulation with thrombin at 0.03 U/ml or higher, while TXB2 synthesis was increased by thrombin at 0.1 U/ml or higher. The platelet 12(S)-HETE production was increased 10 s after stimulation and this was earlier than CD62 expression. The expression of CD62 was inhibited by the lipoxygenase (LOX) inhibitors quercetin and nordihydroguaiaretic acid but was not affected by the cyclooxygenase (COX) inhibitors aspirin and indomethacin. Exogenously added 12(S)-HPETE and 12(S)-HETE enhanced CD62 expression, but other HETEs did not. Consequently, 12-LOX products play a role in the expression of CD62 and could be a second messenger for platelet activation.