Synergism of tumor necrosis factor and interferon-γ in induction of differentiation of human myeloblastic leukemic ML-1 cells

Abstract

Natural or recombinant human tumor necrosis factor (TNF) induced NBT-reducing activity of ML-1 cells in a dose-dependent manner. Interferon-γ (IFN-γ) induced NBT-reducing activity only marginally. However, when IFN-γ was combined with TNF, induction of NBT-reducing activity was remarkably increased. IFN-α or -β had almost no effect on the induction of NBT-reducing activity of ML-1 cells, either alone or in combination with TNF. Treatment with both TNF and IFN-γ synergistically enhanced morphological changes, growth inhibition and activity of Fc receptors, and NBT reduction in ML-1 cells, but not phagocytic activity. The TNF treated cells were classified as macrophage-like by morphology, and by lineage-specific α-naphthyl acetate esterase stain. The results indicate that combinations of TNF and IFN-γ act synergestically in the induction of differentiation of human myeloblastic ML-1 cells.