A combination of a T cell-derived lymphokine differentiation-inducing activity and a physiologic concentration of retinoic acid induces HL-60 to differentiate to cells with functional chemotactic peptide receptors

The human acute promyelocytic leukemia cell line HL-60 is induced by retinoic acid (RA) and N,N-dimethylformamide (DMF) to differentiate into cells having many of the functional and morphologic characteristics of mature granulocytes. With normal human phagocytic cells there is both superoxide anion (O2-) production and chemotaxis in response to chemoattractants such as N-formyl-methionyl-leucyl- phenylalanine (FMLP). We have now found that although HL-60 cells induced with RA alone produce O2- in response to 12-0-tetradecanoyl- phorbol-13-acetate (TPA) they are deficient in FMLP-stimulated O2- production and chemotaxis. In contrast, HL-60 induced either with DMF or with a combination of 10 nmol/L RA and a T cell-derived lymphokine, differentiation-inducing activity (DIA), produce O2- and exhibit chemotaxis in response to FMLP. The basis for these results appears to be the concentration of cell surface chemotactic peptide receptors. Thus, untreated HL-60 and HL-60 induced with either RA alone or DIA alone do not have measurable levels of FMLP receptors, whereas HL-60 induced with a combination of RA and DIA has 5,400 receptors per cell. HL-60 induced with RA and DIA plus 1 mumol/L dexamethasone have 25,000 receptors per cell and have greater chemotactic activity than HL-60 induced with the combination of RA and DIA. Thus, differentiation of HL- 60 to cells with many properties of normal phagocytes can be induced in vitro by physiologic substances.