Granulocyte functions during maturation of human promyelocytic leukemia cells

Human promyelocytic leukemia cells (HL-60) mature into functional granulocytes in response to in vitro treatment with several classes of chemical agents. Compounds that increase intracellular adenosine 3':5' -cyclic monophosphate induce a modified program of maturation in which the cells demonstrate functional properties characteristic of mature phagocytic cells while remaining morphologically immature. We compared the developmental programs initiated by two well-studied inducers, retinoic acid and dimethyl sulfoxide, with the programs initiated by two inducers known to raise intracellular adenosine 3':5' -cyclic monophosphate; N6, O2-dibutyryl adenosine 3':5' -cyclic monophosphate and the combination of prostaglandin E2 and theophylline. In response to the increase in intracellular adenosine 3':5' -cyclic monophosphate, the cells ceased proliferation, expressed chemotactic receptors and demonstrated stimulated enzyme release within 24 h. Chemotaxis, adherence, NBT reduction and superoxide production appeared by 72 h, although the cells remained unchanged morphologically. A similar developmental program was induced by dimethylsulfoxide, but appearance of the markers was delayed by 48 h. Expression of these markers was delayed and incomplete in response to retinoic acid.