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Nitric oxide and infectious diseases
  1. David Burgner,
  2. Kirk Rockett,
  3. Dominic Kwiatkowski
  1. Molecular Infectious Diseases Group, Department of Paediatrics, University of Oxford, Level 4, John Radcliffe Hospital, Oxford OX3 9D, UK
  1. Dr Burgner. email: dburgner{at}molbiol.ox.ac.uk

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Nitric oxide (NO) has undergone something of an image change in recent years. Previously considered a pollutant from car exhausts, NO has now been implicated in many physiological processes. Here we review the dual roles of NO in infection—as a critical agent of host defence but also as a central mediator of pathogenesis—using septic shock, bacterial meningitis, and malaria to illustrate some current concepts and controversies. We have limited our discussion of the important physiological functions of NO in the cardiovascular and neurological systems to instances where these impinge on its role in infectious diseases.

NO is formed by the oxidative deamination of the amino acid L-arginine by nitric oxide synthases (NOS) (fig 1). Three isoforms of this enzyme are described (table 1).1 Neuronal NOS (nNOS or NOS1) is constitutively present in both the central and peripheral nervous systems, where NO acts as a neurotransmitter. Endothelial NOS (eNOS or NOS3) is constitutively expressed by endothelium and other cell types and is involved in cardiovascular homeostasis. In contrast, inducible NOS (iNOS or NOS2) is absent in resting cells, but the gene is rapidly expressed in response to stimuli such as proinflammatory cytokines. Once present, iNOS synthesises 100–1000 times more NO than the constitutive enzymes and does so for prolonged periods; the production of NO by eNOS and nNOS has been likened to a dripping tap, while that by iNOS to a fire hose. This high concentration of NO may inhibit a large variety of microbes, but may also potentially damage the host, thereby contributing to pathology.

Figure 1

Conversion of L-arginine to L-citrulline plus nitric oxide as catalysed by nitric oxide synthases. Two primary steps have been identified. The first step, a two electron oxidation, is a hydoxylation of one of the guanidino nitrogens of L-arginine requiring molecular oxygen and nicotinamide …

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