Nitric oxide: a protective or pathogenic molecule?

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Nitric oxide is a labile molecule involved in a diverse range of biological functions including host defence against infection by pathogens. Oxidative deamination of the amino acid L-arginine, catalysed by a group of enzymes called nitric oxide synthases, results in the formation of L-citrulline and nitric oxide. A large number of pathogens, including bacteria, yeasts and multicellular parasites are susceptible to nitric oxide-mediated toxicity in vitro suggesting that nitric oxide is potentially an important molecule in host defence. Recent studies in vivo have demonstrated that infection of a host by micro-organisms can result in the induction of nitric oxide synthase, release of high levels of nitric oxide by inflammatory cells and resolution of the infection. However, the persistent production of high levels of nitric oxide in chronic disease states, can result in immune suppression, pathological changes and even host death. Whether nitric oxide is predominantly an immunoprotective or host-damaging agent, following infection, may depend on the host-pathogen equilibrium. This review discusses the role of nitric oxide both as a protective and pathogenic molecule in disease.

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