Enhancement of mononuclear procoagulant activity by platelet 12-hydroxyeicosatetraenoic acid

Platelets induce generation of procoagulant tissue factor activity (TFa) by mononuclear leukocytes, and also enhance the TFa induced by endotoxin. Our present investigation demonstrated that arachidonic acid, which by itself had no effect on mononuclear TFa, greatly enhanced platelet-induced TFa. The effect was concentration dependent for both platelets and arachidonate (1-20 microM); other fatty acids tested were inactive. The enhancing effect of arachidonate was more pronounced if platelets were exposed to aspirin, suggesting lipoxygenase product involvement. Production of 12-hydroxyeicosatetraenoic acid (12-HETE) was demonstrated biochemically in aspirin-treated platelet/arachidonate/mononuclear cell preparations that generated high levels of TFa. The enhancing role of 12-HETE was verified as follows. Addition of platelet-derived or synthetic 12-HETE amplified endotoxin-induced TFa more than threefold. Other lipoxygenase products were inactive. Enhancement of mononuclear cell TFa by 12-HETE represents a newly described biological function for this eicosanoid in cell-cell interactions between platelets and mononuclear cells.