Modulation of Retinoic Acid-induced Differentiation of Human Leukemia (HL-60) Cells by Serum Factors and Sphinganine1

The human cell line HL-60 was used to investigate the role of protein kinase C in the regulation of retinole acid-induced maturation of promyelocytic leukemia cells by growth and differentiation factors found in serum. Cells grown in serum-containing medium differentiated less than cells in serum-free medium due to several factors, including albumin binding of retinoic acid. Addition of an inhibitor (sphinganine) of protein kinase C, an enzyme that participates in cellular responses to many serum factors, facilitated the retinoic acid-induced differentiation. Cells treated with both retinoic acid and sphinganine produced more Superoxide when stimulated by formylmethionylleucylphenylalanine; hence, this combi nation generated a more functional population of cells. The ability of sphinganine to promote retinoic acid-induced differentiation suggests that retinoic acid therapy might be improved by the concurrent use of a modulator of protein kinase C activity.