Monohydroxyeicosatetraenoic acids (HETEs) induce degranulation of human neutrophils

Abstract

5-S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), a lipoxygenase product in neurophils, and 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), a lipoxygenase product in platelets, were prepared biosynthetically and incubated with purified human peripheral neutrophils. Both 5-HETE and 12-HETE at 5- to 10-microM concentrations induced degranulation of specific granules. Both 5-HETE and 12-HETE are chemotactic for neutrophils at these concentrations. Arachidonic acid, the metabolic precursor of 5-HETE and 12-HETE, did not induce degranulation. The calcium ionophore A23187 induces neutrophils degranulation and also activates arachidonic acid metabolism in neutrophils resulting in 5-HETE production. Both ionophore-induced 5-HETE production and ionophore-induced degranulation can be inhibited, with very similar inhibition curves, by 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonate metabolism. We propose that the mechanism for 5-HETE- and 12-HETE-induced degranulation is an alteration in the fatty acid composition of membrane phospholipids.