Cellular Mechanisms of Nonspecific Immunity to Intracellular Infection: Cytokine-Induced Synthesis of Toxic Nitrogen Oxides from L-Arginine by Macrophages and Hepatocytes.

摘要

Nitric oxide (NO) produced by cytokine-treated macrophages and hepatocytes plays a vital role in protective host responses to infectious pathogens. NO inhibits iron-sulfur-dependent enzymes involved in cellular respiration, energy production, and reproduction. Synthesis of L-arginine-derived nitrite (NOsub2), the oxidative end product of NO, directly correlates with intracellular killing of Leishmania major, an obligate intracellular protozoan parasite of macrophages: the level of NOsub2 production is a quantitative index for macrophage activation. The competitive inhibitor of NO synthesis, monomethylarginine (NMMLA), inhibits both parasite killing and NOsub2 production. For Leishmania, the parasite itself participates in the regulation of this toxic effector mechanism. (js)