Bacterial infection induces nitric oxide synthase in human neutrophils.
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.
Wheeler
M A
MA
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Smith
S D
SD
García-Cardeña
G
G
Nathan
C F
CF
Weiss
R M
RM
Sessa
W C
WC
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001424:Bacterial Infections / Q000201:enzymology* / Q000652:urine; D015153:Blotting, Western; D002172:Canavanine / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects / Q000302:isolation & purification; D019335:Nitroarginine / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000201:enzymology* / Q000652:urine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D006146:Guanidines; D007527:Isoenzymes; D012333:RNA, Messenger; D013449:Sulfonamides; C086715:thiocitrulline; D019335:Nitroarginine; D014268:Trifluoperazine; D019323:omega-N-Methylarginine; D002956:Citrulline; C065027:N(G)-iminoethylornithine; D002172:Canavanine; C017967:W 7; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D017493:Leukocyte Common Antigens; D013890:Thiourea; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester