A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.
We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; C030722:8,15-leukotriene B4; C034922:5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid