Up-regulation of gamma interferon receptors on the human monocytic cell line U937 by 1,25-dihydroxyvitamin D3 and granulocyte-macrophage colony stimulating factor

The human monoblast-like cell line U937 can be induced to differentiate by a variety of agents including phorbol esters, retinoic acid, gamma interferon (IFN γ), and 1,25-dihydroxyvitamin D3 (VD3). Increased expression of OKM1 antigen, Fc receptors, and other cell surface antigens occur with the differentiation of this cell line along the macrophage lineage. Whereas 10^-8 M VD3 alone induces changes in cell surface antigens there were no changes in the number of affinity of IFN γ receptors. Incubation of U937 with VD3 and 100 U/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in further increases in OKM1 antigen expression and an up-regulation of IFN γ receptors. The number of IFN γ receptors increased between two- and fourfold and was maximal after 48 h incubation with VD3 and GM-CSF. Scatchard analysis revealed a single class of receptors before or after differentiation, although the increase in receptor number was associated with an overall decrease in receptor-binding affinity. Incubation of U937 with VD3 plus GM-CSF and IFN γ resulted in further increases in the density of OKM1 antigen expressed per cell. This increase in OKM1 expression was greater than that observed for U937 incubated with VD3 and GM-CSF or VD3 and IFN γ alone. These results suggest that GM-CSF up-regulates IFN γ receptors on VD3-stimulated U937 and enables these cells to be induced further along the pathway of macrophage differentiation, possibly by subsequent interaction with additional cytokines such as IFN γ.