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 interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS), their synthesis of peroxynitrite and their cytostatic activity against mouse lymphocytic leukemia (L1210) cells were examined. The activation of the genes for nitric oxide synthase (iNOS) and heme oxygenase (HO-1) was also determined during the activation of the macrophages. Results showed that activation of peroxynitrite synthesis in macrophages was accompanied by the transcriptional activation of iNOS and HO-1 genes. Both genes seem to be activated simultaneously upon activation of the macrophages. Simultaneous activation of iNOS and HO-1 genes may be important because degradation of heme by HO-1 is one of the most important reaction that produces CO in higher organisms, and nitric oxide (NO) and carbon monoxide (CO) can react with heme-containing guanylate cyclase.