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Abstract

The identification of human inflammatory cells that express inducible nitric oxide synthase and the clarification of the role of inducible nitric oxide synthase in human infectious or inflammatory processes have been elusive. In neutrophil-enriched fractions from urine, we demonstrate a 43-fold increase in nitric oxide synthase activity in patients with urinary tract infections compared with that in neutrophil-enriched fractions from noninfected controls. Partially purified inducible nitric oxide synthase is primarily membrane associated, calcium independent, and inhibited by arginine analogues with a rank order consistent with that of purified human inducible nitric oxide synthase. Molecular, biochemical, and immunocytochemical evidence unequivocally identifies inducible nitric oxide synthase as the major nitric oxide synthase isoform found in neutrophils isolated from urine during urinary tract infections. Elevated inducible nitric oxide synthase activity and elevated nitric oxide synthase protein measured in patients with urinary tract infections and treated with antibiotics does not decrease until 6-10 d of antibiotic treatment. The extended elevation of neutrophil inducible nitric oxide synthase during urinary tract infections may have both antimicrobial and proinflammatory functions.

Authors

M A Wheeler, S D Smith, G García-Cardeña, C F Nathan, R M Weiss, W C Sessa

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Citations to this article in year 2008 (5)

Title and authors Publication Year
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LK Harris, J McCormick, JE Cartwright, GS Whitley, PR Dash
Experimental Cell Research 2008
NO-donors. Part 171: Synthesis and antimicrobial activity of novel ketoconazole–NO-donor hybrid compounds
J Konter, U Möllmann, J Lehmann
Bioorganic & Medicinal Chemistry 2008
Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis
WE Roediger
Alimentary Pharmacology & Therapeutics 2008
Contribution of free radicals to Pseudomonas aeruginosa induced acute pyelonephritis
R Mittal, S Sharma, S Chhibber, K Harjai
Microbial Pathogenesis 2008

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