Macrophage precursors grow and differentiate in response to specific growth factors. We have found that the simultaneous expression of two oncogenes (v-myc and v-raf) in fresh murine both marrow derived macrophages, induces the selective growth of macrophages in the absence of exogenous or endogenous growth factors. Utilizing this experimental system macrophage cell lines have been established, and we have demonstrated that these cell lines are similar to normal macrophages in many functional activities including the expression of Ia antigen and of tumoricidal activity. Extensive studies of the molecular basis for activation of macrophages to a tumoricidal stage have revealed that the intracellular levels of 5-adenosylmethionine and of ribosomal RNA (rRNA) precursors play a major role in the control of macrophage functions. Since rRNA precursors have double stranded structures they can directly activate double-stranded dependent enzymes which, in turn regulate the proteosynthetic activity of the cells. This activity of rRNA precursors is related to the expression of tumoricidal activity by macrophages. Among the early events that are involved in macrophage activation we have identified the augmentation of the expression of the protooncogene c-fos. It has been proven that in macrophages, c-fos expression is under direct control of protein kinase-c, and may lead to the expression of macrophage functional activities.
