Role of nitric oxide in the failure of neutrophil migration in sepsis.
The cecal ligation and puncture (CLP) model was used to investigate whether failure of neutrophil migration occurs in sepsis and whether it correlates with disease outcome. It was observed that the severity of sepsis correlates with the number of punctures in the cecum: mice with 2 punctures (sublethal [SL]-CLP) developed mild peritonitis (100% survived), whereas mice with 12 punctures (lethal [L]-CLP) developed severe peritonitis and bacteremia that evolved to sepsis (none survived). The production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-10 was higher in L-CLP than in SL-CLP mice. The impairment of neutrophil migration to the peritoneum and to the cecum wall was observed only in L-CLP mice. This phenomenon was shown to be mediated by nitric oxide, because aminoguanidine prevented the failure of neutrophil migration and improved the survival of L-CLP animals. In conclusion, impairment of neutrophil migration is a crucial event in the worsening of sepsis, and nitric oxide seems to be responsible for the phenomenon.
Benjamim
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Department of Pharmacology, Faculty of Medicine Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Ferreira
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D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D016470:Bacteremia / Q000209:etiology; D002465:Cell Movement; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D019335:Nitroarginine / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000293:injuries* / Q000382:microbiology; D010532:Peritoneal Diseases / Q000382:microbiology; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014950:Wounds, Penetrating
D016207:Cytokines; D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine