Regulation of HL-60 differentiation by lipoxygenase pathway metabolites in vitro.
We have studied the effects of lipoxygenase inhibition and metabolite addition of HL-60 cells induced to differentiate. When HL-60 are induced by dimethyl sulfoxide (DMSO) in the presence of an inhibitor of lipoxygenase, caffeic acid, there is a marked change from the expected phenotype of mature granulocytes to a population composed predominantly of mature monocytes. (DMSO alone: 54% granulocytes, 10% monocytes; DMSO + caffeic acid: 23% granulocytes, 53% monocytes.) Addition of leukotriene D4 to DMSO-induced, caffeic acid-inhibited cultures resulted in a dose-dependent recovery of the granulocyte phenotype. Addition of lipoxygenase inhibitors to phorbol ester-treated HL-60 cells did not alter the expected monocytic differentiation. These results support a role for leukotriene D4 in the regulation of granulocyte differentiation of HL-60 cells induced with DMSO.
Miller
A M
AM
University of Florida, College of Medicine, Gainesville 32610.
Kobb
S M
SM
McTiernan
R
R
D002109:Caffeic Acids / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006651:Histocytochemistry; D006801:Humans; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D009000:Monocytes / Q000166:cytology; D013189:SRS-A / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002109:Caffeic Acids; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D014212:Tretinoin; D011464:Epoprostenol; D013755:Tetradecanoylphorbol Acetate; C035296:piriprost; C040048:caffeic acid; D004121:Dimethyl Sulfoxide