Control of macrophage cell differentiation in human promyelocytic HL-60 leukemia cells by 1,25-dihydroxyvitamin D3 and phorbol-12-myristate-13-acetate.
Human promyelocytic leukemia cells (HL-60) were induced to differentiate into macrophage-like cells in a dose (3 X 10(-10) to 10(-7) M) and time (1 to 6 days)-dependent manner by 1,25-dihydroxyvitamin D3 and the tumor promoter, phorbol-12-myristate-13-acetate. Differentiation was determined by an increase in the percentage of morphologically mature cells, in lysozyme and nonspecific esterase activities, and in reactivity with the murine OKM1 monoclonal antibody. Two HL-60 cell variants, designated as R-80 and B-II, were also examined. R-80 cells, which are resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate, also exhibited resistance, although to a lesser degree, to induction of cell differentiation by 1,25-dihydroxyvitamin D3. The resistance to the action of the two compounds is presumably not due to similar binding sites for the two inducers, since 1,25-dihydroxyvitamin D3 was unable to compete for the phorbol diester binding sites as measured by [3H]phorbol-12,13-dibutyrate binding. B-II cells were resistant to induction of cell differentiation by 1,25-dihydroxyvitamin D3, phorbol-12-myristate-13-acetate, retinoic acid, and dimethyl sulfoxide. Two-dimensional electrophoretic analysis of HL-60 cell protein patterns indicated that treatment of the HL-60 cells with 1,25-dihydroxyvitamin D3, phorbol-12-myristate-13-acetate, retinoic acid, and dimethyl sulfoxide caused the cells to express various monocyte-macrophage and granulocyte marker proteins. None of the inducers caused a protein pattern identical to that of peripheral monocytes or granulocytes in the HL-60 cells, but the protein pattern of the HL-60 cells treated with 1,25-dihydroxyvitamin D3 was the closest to that of peripheral blood monocytes. These results indicate that 1,25-dihydroxyvitamin D3 induces in the HL-60 cells a phenotype that resembles, but is not identical to, that of peripheral monocytes-macrophages.
D000911:Antibodies, Monoclonal; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D010704:Phorbols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D010703:Phorbol Esters; D010704:Phorbols; D015240:Phorbol 12,13-Dibutyrate; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide