Enrichment of human platelet phospholipids with linoleic acid diminishes thromboxane release

We have investigated whether exposure of human platelets to elevated concentrations of linoleic acid, the principal dietary polyunsaturate, would influence platelet thromboxane A2 release. Platelets were incubated with albumin-bound linoleic acid at 30 degrees C for 24 h, with prostaglandin E1 added to prevent aggregation. The linoleic acid supplemented platelets released, on average, 50% less thromboxane A2 in response to stimulation with thrombin than corresponding control platelets. Other fatty acids were without appreciable effect. The inhibition of thrombin-stimulated thromboxane A2 release was dependent on the time and temperature of incubation, as well as on the concentration of added linoleic acid. Supplementation increased the amount of linoleic acid in the platelet phospholipids, but the arachidonic acid content of the phospholipids was reduced. [1-14C]Linoleic acid was not converted to arachidonic acid by the platelets. Linoleic acid was released exclusively from the inositol phosphoglycerides when the enriched platelets were stimulated with thrombin. The linoleate-enriched platelets converted less [1-14C]arachidonic acid to all prostaglandin products, suggesting that the platelet cyclooxygenase was partially inhibited.