The most important and novel aspect that we have analyzed is the response of macrophages and monocytes through the Beta-chain of the IL-2 receptor (IL-2RBeta) that is constitutively expressed on circulatory cells. In contrast induction of IL-2RBeta by IFNgamma is needed to render murine macrophages susceptible to activation by interleukin 2. Studies on the molecular response elicited by IL-2 in monocytic cells revealed that IL-2 induced augmentation of the IL-2RBeta without affecting IL-2Ralpha expression. Induction of IL-6 and CSFI receptor was also associated to monocyte activation by IL-2. Synergism between IL-2 and IFNgamma or CSFI has been observed in the activation of cytotoxic activity. In contrast, inhibitory effects on the activation by IL-2 are exerted by IL-4 and TGFBeta. The interaction between IL-2 and other cytokine is being analyzed at the levels of nuclear transactivating factors. During the course of these studies the modulation by IFNgamma of transactivating factors involved in the expressing of IL-2Ralpha chain has been established. Moreover, a new DNA binding protein recognizing the HIV-LTR as well as the IL-2 receptor alpha-chain is being cloned. Studies on the modulation of DNA binding proteins are also in progress to determine the mechanisms by which IFNgamma can inhibit macrophage functions (c-fos mRNA expression, induction of IL-6 by IL-1) under certain conditions. Finally we have extensively analyzed the expression and the role of double stranded RNA-dependent enzymes in the activation of murine macrophages. The results are consistent with the hypothesis of a central role for these enzymes in the late phases of macrophage activation, and lead to the discovery of the unique macrophage activating properties of picolinic a metabolite of tryptophan. These results provided the first evidence of a direct role of tryptophan metabolites in macrophage activities.
