PMID- 15962127
OWN - NLM
STAT- MEDLINE
DCOM- 20051214
LR  - 20190606
IS  - 0074-0276 (Print)
IS  - 0074-0276 (Linking)
VI  - 100 Suppl 1
DP  - 2005 Mar
TI  - Failure of neutrophil migration toward infectious focus in severe sepsis: a 
      critical event for the outcome of this syndrome.
PG  - 223-6
AB  - 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.
FAU - Alves-Filho, Jose Carlos
AU  - Alves-Filho JC
AD  - Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, USP, 
      Ribeirao Preto, SP 14049-900, Brasil.
FAU - Benjamim, Claudia
AU  - Benjamim C
FAU - Tavares-Murta, Beatriz Martins
AU  - Tavares-Murta BM
FAU - Cunha, Fernando Q
AU  - Cunha FQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050614
PL  - Brazil
TA  - Mem Inst Oswaldo Cruz
JT  - Memorias do Instituto Oswaldo Cruz
JID - 7502619
RN  - 0 (Cytokines)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Cell Movement/immunology/*physiology
MH  - Cytokines/*biosynthesis
MH  - Humans
MH  - Mice
MH  - Neutrophils/immunology/*physiology
MH  - Nitric Oxide/*biosynthesis
MH  - Severity of Illness Index
MH  - Systemic Inflammatory Response Syndrome/*immunology/physiopathology
EDAT- 2005/06/18 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/06/18 09:00
PHST- 2005/06/18 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/06/18 09:00 [entrez]
AID - S0074-02762005000900038 [pii]
AID - 10.1590/s0074-02762005000900038 [doi]
PST - ppublish
SO  - Mem Inst Oswaldo Cruz. 2005 Mar;100 Suppl 1:223-6. doi: 
      10.1590/s0074-02762005000900038. Epub 2005 Jun 14.