The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs)

Abstract

The lipoxygenation of arachidonic acid in basophils, mastocytoma cells, and other leukocytes generates the unstable intermediate 5-hydroperoxy-eicostaetraenoic acid, which is converted in part to a series of complex hydroxy-eicosatetraenoic acids (HETEs) with additional polar substituents and 3 conjugated double bonds. One of the products, 5,12-di-HETE, is chemotactic for human neutrophils in vitro at a concentration as low as 3 ng/ml and evokes a maximal neutrophil chemotactic response at 30 ng/ml, as compared to 1000 ng/ml for 5-HETE and 10,000 to 20,000 ng/ml for 11-HETE and 12-HETE. In contrast, other products in the same series, such as the slow reacting substance 5-hydroxy-6-glutathionyl-eicosatetraenoic acid (leukotriene C), and the platelet-derived 8,9,12-trihydroxy-eicosatrienoic acid and 8,11,12-trihydroxy-eicosatrienoic acid exhibited only marginal neutrophil chemotactic activity. Only 5,12-di-HETE released significant quantities of beta-glucuronidase and lysozyme from the neutrophils, but the maximal level of enzyme release was far less than that for the chemotactic fragment of C5 and the formyl-methionyl peptides.