Eicosanoid Metabolism in Human Platelets is Modified by Albumin

Activation of human platelets leads to release of arachidonic acid from cellular phospholipids, the step which is believed to be the rate limiting for the metabolism of this fatty acid. Once released arachidonic acid can be metabolised by two platelet enzymes. Cyclooxygenase produces endoperoxides with the subsequent formation of thromboxane A2 (TXA2). Another enzyme, 12-lipoxygenase, catalyses conversion of arachidonic acid to 12-hydroperoxyeicosatetraenoic acid (12-HPETE) which is rapidly reduced to 12-hydroxyeico-satetraenoic acid (12-HETE)1. The physiological significance of the latter pathway is poorly understood to date. Previously we have shown that albumin prevents metabolism of 12-HETE by polymorphonuclear leukocytes in vitro and protects it from metabolism by blood cells in vivo 2,3. In the present study we have investigated the influence of albumin on the activity of 12-lipoxygenase in the presence of phospholipase A2 and C inhibitors. In addition, we studied the influence of 15-hydroxyeicosatetraenoic acid (15-HETE), which has been reported to be a selective platelet 12-lipoxygenase inhibitor4, and 5-hydroxyeico-satetraenoic acid (5-HETE), which is a substrate for 12-lipoxygenase, on the endogenous 12-HETE production in the presence of albumin.