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.

DESIGN:

Laboratory investigation.

SETTING:

Research laboratory at Rouen University Medical School.

SUBJECTS:

Male wild-type, TLR4(-/-) and TLR2(-/-) mice with the same C57BL/6 background.

INTERVENTIONS:

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.

MEASUREMENTS AND MAIN 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: Ygal Benhamou, Julie Favre, Philippe Musette, Sylvanie Renet, Christian Thuillez, Vincent Richard, Fabienne Tamion
• Journal: Critical care medicine (Crit Care Med) Vol. 37 Issue 5 Pg. 1724-8 (May 2009) ISSN: 1530-0293 [Electronic] United States
• PMID: 19325486 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endotoxins
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Disease Models, Animal
• Endothelium, Vascular (metabolism, pathology)
• Endotoxins (analysis)
• Male
• Mesenteric Arteries (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Probability
• Random Allocation
• Resuscitation (methods, mortality)
• Sensitivity and Specificity
• Shock, Hemorrhagic (immunology, pathology, therapy)
• Signal Transduction (drug effects, physiology)
• Survival Rate
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Vasculitis (metabolism, pathology)