INDUCTION OF ESSENTIAL COMPONENTS OF THE SUPEROXIDE GENERATING-SYSTEMIN HUMAN MONOBLASTIC LEUKEMIA U937 CELLS

Cytochrome b(558) composed of large and small subunits, and cytosolic 47- and 65-kDa proteins are important constituents of the superoxide ( O-2(-)) generating system in phagocytes and B lymphocytes. In this pap er, me describe changes in O-2(-)-generating activity and expression o f O-2(-)-generating components during differentiation of human monobla stic leukemia U937 cells to macrophage-like cells. Undifferentiated U9 37 cells generated no O-2(-) in response to a stimulation, although th ey expressed the three components other than the cytochrome b(558) lar ge subunit. When U937 cells were cultured with agents that induced the cell differentiation, such as vitamin D-3, retinoic acid, interferon- gamma, and tumor necrosis factor, O-2(-)-generating activity increased 5- to 200-fold depending on the agent used. Immunoblotting analysis r evealed that the amounts of the four protein components essential for O-2(-) generation increased, although their induction levels were sign ificantly different between inducers. Among the four protein component s, the cytochrome subunits mere induced in low levels by all agents te sted, which may explain why the O-2(-)-generating activity of differen tiated U937 cells was much lower than that of neutrophils from periphe ral blood.