Hemorrhage-induced acute lung injury is TLR-4 dependent.
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.
Barsness
Katherine A
KA
Department of Surgery, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Box C320, Denver, CO 80262, USA. katherine.barsness@uchsc.edu
Arcaroli
John
J
Harken
Alden H
AH
Abraham
Edward
E
Banerjee
Anirban
A
Reznikov
Leonid
L
McIntyre
Robert C
RC
D000208:Acute Disease; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism; D006470:Hemorrhage / Q000150:complications* / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D010539:Permeability; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha