Potentiating actions of hydroxyeicosatetraenoates on human neutrophil degranulation responses to leukotriene B4 and phorbol myristate acetate

Abstract

Previous studies demonstrated that the arachidonate metabolite, 5-L-hydroxy-6,8,11,14-eicosatetraenoate (5-L-HETE), potentiates the human polymorphonuclear neutrophil degranulation response to platelet-activating factor without influencing this response when elicited by C5a, a formylated oligopeptide, or ionophore A23187. We now find that the HETE amplifies the degranulation response to phorbol myristate acetate and leukotriene B4. The HETE was active in dosages as low as 50 nM; at 5 μM, it produced 1000-, 30-, and 5-fold enhancements in the potencies of platelet-activating factor, phorbol myristate acetate, and leukotriene B4, respectively. 5-rac-HETE had similar actions but 8-rac-HETE, 9-rac-HETE, and 12-L-HETE possessed little or no effects. Thus, 5-L-HETE potentiates the actions of various structurally unrelated degranulating agents; it particularly influences those compounds which, like 5-L-HETE itself, are formed by stimulus-activated neutrophils, viz., leukotriene B4 and platelet-activating factor. These latter two lipids and 5-L-HETE may interact to mediate neutrophil degranulation responses.