U937 cell line: impact of CSFs, IL-6 and IFN-gamma on the differentiation and the Leu-CAM proteins expression.

Differentiation of the U937 cell line can be induced by various agents. We have investigated the differentiation abilities of gamma-interferon (IFN-gamma), interleukin-6 (IL-6), macrophage and granulocyte-macrophage colony-stimulating factors (M-CSF + GM-CSF) or the combinations IL-6 + M-CSF + GM-CSF and IFN-gamma + M-CSF + GM-CSF on the U937 cells by studying the morphology, cytochemical activity and several functional properties. The expression of the Leu-CAM proteins (CD11a, CD11b, CD11c, CD18) was also evaluated during the culture period. Our results show that the cytokines used in this study inhibit to a certain extent the proliferation of the tumor cells and drive the cells toward a differentiation phenotype that has several characteristics in common with mononuclear phagocytes, such as the expression of CD14, phagocytosis and release of superoxide anions. The adhesion molecules CD11b alpha chain and CD18 beta chain were strongly induced on the U937 cells with a maximal expression of the CD11b on the cells cultured with either M-CSF + GM-CSF or the combinations of IL-6 and IFN-gamma with M-CSF + GM-CSF. Conversely, for CD11a and CD11c alpha chains a rather low enhancement of the expression was noticed. In our culture system, cells incubated with the combination of M-CSF + GM-CSF exhibited differentiation characteristics which appeared to be largely potentialized when cytokines such as IL-6 or IFN-gamma were added.