Metabolism of Arachidonic Acid by 12- and 15-Lipoxygenases in Human Platelets and Polymorphonuclear Leukocytes
The metabolism of arachidonic acid by human polymorphonuclear leukocytes and indomethacin-treated washed human platelets was investigated. [1-14C]-arachidonic acid (AA) was extensively converted to mono-HETEs and DHETEs in these cell types. These mono-HETEs and DHETEs were identified as oxidative products of AA via the 12- and 15-lipoxygenase pathways and DHETEs were exclusively generated from 15-lipoxygenase pathway. Incubation of AA or 12-Ls-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (12-HETE) with suspensions of human polymorphonuclear leukocytes led to the formation of 12-Ls, 20-dihydroxy-5, 8, 10, 14-eicosatetraenoic acid (12, 20-DHETE). The structure of this new metabolite was assigned by physical methods and by chemical degradation. Thus, during platelet and leukocyte interaction, “transcellular metabolism” of various lipoxygenase products of AA may generate new compounds of biological importance.
KeywordsArachidonic Acid Human Platelet Arachidonic Acid Metabolite Washed Platelet Human Polymorphonuclear Leukocyte
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