Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome
Mem. Inst. Oswaldo Cruz
;
100(supl.1): 223-226, Mar. 2005. graf
Article
Dans Anglais
| LILACS
| ID: lil-402204
RESUMO
Sepsis is a systemic inflammatory response commonly caused by bacterial infection. We demonstrated that the outcome of sepsis induced by cecal ligation and puncture (CLP) correlates with the severity of the neutrophil migration failure towards infectious focus. Failure appears to be due to a decrease in the rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil migration impairment is mediated by the circulating inflammatory cytokines, such as TNF-alpha and IL-8, which induce the nitric oxide (NO) production systemically. It is supported by the fact that intravenous administration of these cytokines reduces the neutrophil migration induced by different inflammatory stimuli, and in severe sepsis the circulating concentrations of the cytokines and chemokines are significantly increased. Moreover, the neutrophil migration failure and the reduction in the rolling/adhesion were not observed in iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was also observed that circulating neutrophils obtained from septic patients present failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in sepsis, failure of neutrophil migration is critical for the outcome and that NO is involved in the process.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Mouvement cellulaire
/
Cytokines
/
Syndrome de réponse inflammatoire généralisée
/
Granulocytes neutrophiles
/
Monoxyde d'azote
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Mem. Inst. Oswaldo Cruz
Thème du journal:
Médecine tropicale
/
Parasitologie
Année:
2005
Type:
Article
Pays d'affiliation:
Brésil
Institution/Pays d'affiliation:
Faculdade de Medicina do Triângulo Mineiro/BR
/
Universidade de São Paulo/BR
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