LEUKOTRIENE-B4 IS A POTENT AND STEREOSPECIFIC STIMULATOR OF NEUTROPHIL CHEMOTAXIS AND ADHERENCE

Abstract

The effects of leukotrienes on in vitro functions of [human] neutrophil polymorphonuclear (PMN) granulcoytes were studied. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10-6 M; 2 nonenzymatically formed isomers (compounds I and II) induced this response at 10-5M. Leukotriene C4 (LTC4) and 5-hydroxyeicosatetraenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with fMet-Leu-Phe (fMLP) at 10-7M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aureus. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 .times. 10-7M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at .gtoreq. 2.5 .times. 10-5M, but not at lower concentrations. Since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, these mediators thus could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.