Effects of nicotine on eicosanoid synthesis of differentiating human promyelocytic leukemia cells.

We studied the conversion of arachidonic acid or prostaglandin H2 into eicosanoids in promyelocytic leukemia cells (HL-60) that were differentiating into macrophages or neutrophils. Our results indicate that several enzymes of eicosanoid synthesis are coordinately and differentially upregulated early in the neutrophil and macrophage differentiation pathways. They also provide evidence for a preferential upregulation of thromboxane synthase in the macrophage differentiation pathway that contrasts with a preferential upregulation of enzymes of the 5-lipoxygenase pathway during neutrophil differentiation. Nicotine at 100 nM selectively inhibited the formation of thromboxane in HL-60 cells induced to differentiate into macrophages. Nicotine therefore alters the pattern of activity of the eicosanoid-synthesizing enzymes in HL-60 cells undergoing macrophage differentiation.