Human natural killer cell activity is reversibly inhibited by antagonists of lipoxygenation.
We here demonstrate that NK cell activity by human peripheral blood mononuclear cells (PBMC) against K562 or MOLT-4 target cells is rapidly and reversibly inhibited by two agents that inhibit the lipoxygenation of fatty acids, BW755C and nordihydroguaiaretic acid (NDGA). Natural killing by nonadherent PBMC was similarly inhibited by both agents, indicating that monocytes were not required for the effect. The inhibition of natural killing was not seen with indomethacin at concentrations that inhibit prostaglandin synthesis but not the lipoxygenation of arachidonic acid. Moreover, indomethacin did not alter inhibition by either BW755C or NDGA. Thus, suppression of natural killing by these agents was not mediated by the effects on prostaglandin synthesis; neither agent inhibited target cell binding. These results suggest that products of lipoxygenation are required for target cell lysis by human NK cells.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol; D009000:Monocytes / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011720:Pyrazoles / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002396:Catechols; D007166:Immunosuppressive Agents; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D011451:Prostaglandin-Endoperoxide Synthases