CONCOMITANT TRANSCRIPTIONAL ACTIVATION OF NITRIC-OXIDE SYNTHASE AND HEME OXYGENASE GENES DURING NITRIC OXIDE-MEDIATED MACROPHAGE CYTOSTASIS

During in vitro activation of mouse peritoneal macrophages with interf eron-gamma (IFN-gamma) and lipopolysaccharide (LPS), their synthesis o f peroxynitrite and their cytostatic activity against mouse lymphocyti c leukemia (L1210) cells were examined, The activation of the genes fo r nitric oxide synthase (iNOS) and heme oxygenase (HO-1) was also dete rmined during the activation of the macrophages. Results showed that a ctivation of peroxynitrite synthesis in macrophages was accompanied by the transcriptional activation of iNOS and HO-1 genes, Both genes see m to be activated simultaneously upon activation of the macrophages, S imultaneous activation of iNOS and HO-1 genes may be important because degradation of heme by HO-1 is one of the most important reaction tha t produces CO in higher organisms, and nitric oxide (NO) and carbon mo noxide (GO) can react with heme-containing guanylate cyclase.