15-Hydroxyeicosatetraenoic acid inhibits neutrophil migration across cytokine-activated endothelium.

摘要: 15-hydroxyeicosatetraenoic acid (15-HETE) is an eicosanoid, formed by the actions of 15-lipoxygenase, epoxygenases, and cyclooxygenases on arachidonic acid, whose tissue levels are often elevated during inflammation. The present study demonstrates that 15(S)-HETE a potent inhibitor polymorphonuclear neutrophil (PMN) migration across cytokine-activated endothelium in vitro. rapidly esterified into PMN phospholipids, we report 15-(S)-HETE-remodeled displayed blunted adhesion to, across, human endothelial cells had been activated with either interleukin-1 beta or tumor necrosis factor-alpha Several lines evidence suggested inhibited transmigration attenuating responsiveness to cell-derived platelet-activating factor (PAF). inhibitory action was not restricted profile molecules expressed endothelium. Interleukin-1 induce PAF production endothelium, receptor antagonist. response exogenous dramatically following exposure 15(S)-HETE. Furthermore, 15(S)-HETE-remodeled impaired cytoskeletal responses when stimulated PAF, two pivotal events seemed attenuate inhibiting membrane-associated signal transduction events. In keeping this interpretation, remodeling phospholipids associated sixfold reduction affinity specific high-affinity receptors for their ligand PAF-triggered IP3 generation. contrast, calcium ionophore activators protein kinase C remained intact. These results provide further may be important endogenous PMN-endothelial cell interaction serves limit reverse neutrophil-mediated inflammation vivo.