Hemorrhage-induced acute lung injury is TLR-4 dependent

Am J Physiol Regul Integr Comp Physiol. 2004 Sep;287(3):R592-9. doi: 10.1152/ajpregu.00412.2003. Epub 2004 Apr 8.


Toll-like receptor 4 (TLR-4), initially identified as an LPS receptor, is critical to the signaling of a variety of danger signals, including heat shock protein 60, fibrinogen, and fibronectin. Recent data also suggest that TLR-4 plays a role in determining survival in both endotoxemia and hemorrhagic shock. We hypothesized that a functional TLR-4 would be required for hemorrhage and endotoxin-induced acute lung injury. Hemorrhage- and endotoxin-induced lung TNF-alpha mRNA and protein production, neutrophil accumulation, and protein permeability were dependent on a functional TLR-4. Hemorrhage-induced nuclear factor (NF)-kappaB activation was independent of functional TLR-4, whereas endotoxin-induced activation of NF-kappaB requires a functional TLR-4 for full response. Therefore, we conclude that 1) hemorrhage-induced acute lung injury is TLR-4 dependent and 2) hemorrhage has a different and distinct TLR-4-dependent intracellular activation mechanism compared with endotoxemia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Endotoxemia / metabolism
  • Hemorrhage / complications*
  • Hemorrhage / metabolism
  • Lung / metabolism
  • Lung / physiopathology
  • Lung Diseases / etiology*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • NF-kappa B / metabolism
  • Neutrophil Infiltration
  • Permeability
  • Receptors, Cell Surface / metabolism*
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / metabolism


  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha