Opposite Sensitivity to the Antiproliferative Action of Interferon-α and Granulocyte-Macrophage Colony-Stimulating Factor in Monoblastic U937 Cells

Abstract

Three variants of the human monoblastic cell line U937 with different degrees of sensitivity to the antiproliferative action of interferon-α (IFN-α) were examined for phenotypic differences. The highly IFN-sensitive variant U937-V expressed twice as many IFN-α binding sites as both its IFN-α-resistant derivative U937-VR and the cell line U937 exhibiting a 20-fold reduction in IFN-α sensitivity as compared to U937-V cells. All three variants were IFN-reactive with regard to induction of 2′,5′-oligoadenylate (2-5A) synthetase activity and were similarly sensitive to the growth-inhibiting action of IFN-γ and tumor necrosis factor. Responsiveness to the antiproliferative effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), however, was confined to cell linesU937 and U937-VR. Although expressing a comparable number of GM-CSF receptors, the highly IFN-sensitive variant U937-V was refractory to GM-CSF. Flow cytometry revealed a marked difference in the expression of the antigen CD11b which was detectable on 85% of cells of the U937-V line but only on approximately 25% of cells derived from the U937 and U937-VR lines. Results thus demonstrate opposite sensitivity of U937 cells to the growth-inhibiting action of IFN-α and GM-CSF, apparently dependent on the state of U937 differentiation as determined by expression of the CD11b antigen.