MACROPHAGE PRIMING AND ACTIVATION DURING FIBROSARCOMA GROWTH - EXPRESSION OF C-MYB, C-MYC, C-FOS, AND C-FMS

Macrophages (M phi)(3) function by a two-step process that includes pr iming (induction of cytokine and enzyme mRNA) and activation (producti on of effector molecules). The initial steps in M phi, priming involve the expression of certain proto-oncogenes that regulate expression of other genes. Because tumor growth primes M phi to produce several sup pressor monokines, we determined if cancer induced M phi expression of these proto-oncogenes, Unstimulated peritoneal M phi from tumor-beari ng hosts (TBH) constitutively expressed the proto-oncogenes c-fms, c-f os, c-myc, and c-myb, whereas normal host (NH) M phi had little or no expression of these proto-oncogenes. When M phi were given a 24-h adhe rence priming stimulus, NH M phi expressed c-fms and c-fos at levels e quivalent to TBH M phi constitutive expression. Adherence had little o r no effect on c-fms and c-fos expression in TBH M phi or on NH and TB H M phi c-myc expression, c-myb expression was not induced in NH M phi during adherence and was strongly decreased in TBH M phi. Activation with a 1-h lipopolysaccharide-treatment increased NH and TBH M phi exp ression of c-fms, c-fos, and c-myc, with higher expression of these pr oto-oncogenes in TBH M phi. Activation failed to induce c-myb expressi on in NH M phi and completely inhibited expression in TBH M phi. Becau se c-fms, c-ros, and c-myc are normally expressed early during M phi a ctivation, our results suggest that tumor growth primes M phi by induc ing c-myb is expressed immature and is These observations explain why NH M phi expression of c-myb was not induced and are consistent with r eports that suggest TBH M phi have not reached full developmental matu rity. Tile induction of M phi protooncogene expression during cancer m ay put M phi in a primed state, which leads to earlier and stronger pr oduction of adverse suppressor and cytotoxic molecules.