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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 2004 (4)

Title and authors Publication Year
Antimicrobial reactive oxygen and nitrogen species: concepts and controversies
FC Fang
Nature Reviews Microbiology 2004
Polarized distribution of inducible nitric oxide synthase regulates activity in intestinal epithelial cells
M Rumbo, F Courjault-Gautier, F Sierro, JC Sirard, E Felley-Bosco
The FEBS journal 2004
Cytoprotective response of A1, a Bcl-2 homologue expressed in mature human neutrophils and promyelocytic HL-60 cells, to oxidant stress-induced cell death
CY Liu, PI Chuang, CL Chou, SM Lin, HC Chen, P Chou, YH Liu, CT Yu, CH Wang, HC Lin, HP Kuo
Journal of Biomedical Science 2004
1-α,25-Dihydroxyvitamin D3 regulates inducible nitric oxide synthase messenger RNA expression and nitric oxide release in macrophage-like RAW 264.7 cells
JM Chang, MC Kuo, HT Kuo, SJ Hwang, JC Tsai, HC Chen, YH Lai
Journal of Laboratory and Clinical Medicine 2004

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