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Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome
- Source :
- Memórias do Instituto Oswaldo Cruz, Volume: 100 Supplement 1, Pages: 223-226, Published: MAR 2005, Memórias do Instituto Oswaldo Cruz., Vol 100, Pp 223-226 (2005)
- Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Microbiology (medical)
Chemokine
lcsh:Arctic medicine. Tropical medicine
Endothelium
lcsh:RC955-962
Neutrophils
lcsh:QR1-502
Nitric Oxide
Severity of Illness Index
lcsh:Microbiology
Nitric oxide
Proinflammatory cytokine
sepsis
Sepsis
chemistry.chemical_compound
Mice
nitric oxide
Cell Movement
Medicine
Animals
Humans
Receptor
biology
business.industry
medicine.disease
Systemic Inflammatory Response Syndrome
medicine.anatomical_structure
chemistry
Immunology
biology.protein
TLR4
Cytokines
NEUTROPHIL MIGRATION
business
neutrophil migration
Subjects
Details
- ISSN :
- 00740276
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Memorias do Instituto Oswaldo Cruz
- Accession number :
- edsair.doi.dedup.....efec40fa6b9c7d80bd534996896b6cbc