Fig. 1
Expression of NOS2 and production of NO by mononuclear phagocytes. Transcription of NOS2 mRNA can be enhanced (+) by certain cytokines, growth factors, and microbial components. Transcription and translation of NOS2 mRNA can be diminished (−) by glucocorticoids, TGF-beta, various cytokines, and iron. The enzyme NOS converts L-arginine to nitric oxide and L-citrulline, and it requires NADPH, biopterin, FMN, FAD, oxygen, and heme for activity. Depletion of L-arginine or tetrahy-drobiopterin diminishes activity. L-arginine analogues such as NG-monomethyl-L-arginine block enzyme activity. Nitric oxide can inhibit NOS activity by interacting with and perhaps oxidizing the enzyme’s heme group. Superoxide and oxygen rapidly diminish nitric oxide activity by oxidizing it. Iron, heme, and cobalamins can blunt nitric oxide’s activity by binding nitric oxide to their iron or cobalt. Abbreviations: IFN, interferon; IL, interleukin; CaM, calmodulin; Larg, Larginine.