INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA ENHANCE P60SRC EXPRESSION IN HUMAN MACROPHAGES AND MYELOMONOCYTIC CELL-LINES

We investigated modulation of p60src expression in human mononuclear p hagocytes. By analysis of S-35!methionine-labelled cells we found tha t synthesis of p60src is higher in human monocytes compared to macroph ages derived from in vitro cultivation of monocytes. Western blot anal ysis showed that expression of p60src in monocyte-derived macrophages can be enhanced if monocytes are differentiated into macrophages in th e presence of interferon-gamma (IFN-gamma), or tumor necrosis factor-a lpha (TNF-alpha). Enhanced p60src expression caused by IFN-gamma or TN F-alpha correlated with an enhanced autophosphorylating kinase activit y assayed in anti-p60src immune precipitates. In vivo phosphorylation of p60src and analysis of phosphopeptides by tryptic digestion showed that treatment with cytokines did not affect the pattern of phosphoryl ation of distinct phosphopeptides. The human monocytic cell lines, U93 7 and HL-60, induced to differentiate along the monocytic pathway by I FN-gamma, or a combination of IFN-gamma and TNF-alpha, expressed highe r amounts of the p60src, but not of the p59fyn or p62yes, kinase activ ity. These findings show that p60src is modulated in the course of dif ferentiation of human monocytes to macrophages, and that macrophage-ac tivating cytokines increase p60src expression in human monocyte-derive d macrophages.