Hemorrhage-induced acute lung injury is TLR-4 dependent

Katherine A. Barsness*, John Arcaroli, Alden H. Harken, Edward Abraham, Anirban Banerjee, Leonid Reznikov, Robert C. McIntyre

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


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-α mRNA and protein production, neutrophil accumulation, and protein permeability were dependent on a functional TLR-4. Hemorrhage-induced nuclear factor (NF)-κB activation was independent of functional TLR-4, whereas endotoxin-induced activation of NF-κB 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.

Original languageEnglish (US)
Pages (from-to)R592-R599
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3 56-3
StatePublished - Sep 2004


  • Endotoxin
  • Nuclear factor-κB
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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