title: Toll-like receptors 4 contribute to endothelial injury and inflammation in hemorrhagic shock in mice.
abstract: OBJECTIVE
  Hemorrhagic shock followed by resuscitation (HS/R) promotes organ injury by priming cells of the innate immune system for inflammatory response. Toll-like receptors (TLRs) play an important role in signal transduction in shock/resuscitation conditions. Because proinflammatory mediators are a critical event in mesenteric endothelial injury induced by HS/R, we assessed the role of TLR4 or TLR2 in this setting.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  Research laboratory at Rouen University Medical School.
  
  
  METHODS
  Male wild-type, TLR4(-/-) and TLR2(-/-) mice with the same C57BL/6 background.
  
  
  METHODS
  Mice were submitted to 30 minutes hemorrhagic shock followed by 1 hour resuscitation, after which mesenteric endothelial dysfunction, microvascular injury, and TNF[alpha] production were assessed.
  
  
  RESULTS
  HS/R markedly decreased nitric oxide-mediated mesenteric relaxations induced by acetylcholine, assessed ex vivo on a myograph. By contrast, in TLR4-deficient mice, HS/R did not impair the nitric oxide-mediated responses to acetylcholine. No protection was observed in TLR2-deficient mice. TLR4-deficient mice also displayed a significant reduction in fluid resuscitation and TNF[alpha] systemic production.
  
  
  CONCLUSIONS
  TLR4 contributes to mesenteric endothelial dysfunction after hemorrhagic shock. This early TLR4-induced vascular injury may be an important trigger of the systemic inflammatory response occurring in this disease.
authors.affiliation: Inserm U644, Institute for Biomedical Research and IFRMP 23, Rouen University Medical School, Rouen, France.
authors.forename: Ygal
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Julie
authors.initials: J
authors.lastname: Favre
authors.forename: Philippe
authors.initials: P
authors.lastname: Musette
authors.forename: Sylvanie
authors.initials: S
authors.lastname: Renet
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tamion