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

doi:10.1152/ajpregu.00412.2003

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

Surgery

Research output: Contribution to journal › Article › peer-review

110 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	R592-R599
Journal	American Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume	287
Issue number	3 56-3
DOIs	https://doi.org/10.1152/ajpregu.00412.2003
State	Published - Sep 2004

Keywords

Endotoxin
Nuclear factor-κB
Tumor necrosis factor-α

ASJC Scopus subject areas

Physiology
Physiology (medical)

Access to Document

10.1152/ajpregu.00412.2003

Fingerprint Dive into the research topics of 'Hemorrhage-induced acute lung injury is TLR-4 dependent'. Together they form a unique fingerprint.

Cite this

@article{d8ba6a7bd3674281b1078d2d27717765,

title = "Hemorrhage-induced acute lung injury is TLR-4 dependent",

abstract = "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.",

keywords = "Endotoxin, Nuclear factor-κB, Tumor necrosis factor-α",

author = "Barsness, {Katherine A.} and John Arcaroli and Harken, {Alden H.} and Edward Abraham and Anirban Banerjee and Leonid Reznikov and McIntyre, {Robert C.}",

year = "2004",

month = sep,

doi = "10.1152/ajpregu.00412.2003",

language = "English (US)",

volume = "287",

pages = "R592--R599",

journal = "American Journal of Physiology",

issn = "0363-6119",

publisher = "American Physiological Society",

number = "3 56-3",

}

Hemorrhage-induced acute lung injury is TLR-4 dependent. / Barsness, Katherine A.; Arcaroli, John; Harken, Alden H.; Abraham, Edward; Banerjee, Anirban; Reznikov, Leonid; McIntyre, Robert C.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 287, No. 3 56-3, 09.2004, p. R592-R599.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Hemorrhage-induced acute lung injury is TLR-4 dependent

AU - Barsness, Katherine A.

AU - Arcaroli, John

AU - Harken, Alden H.

AU - Abraham, Edward

AU - Banerjee, Anirban

AU - Reznikov, Leonid

AU - McIntyre, Robert C.

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

KW - Endotoxin

KW - Nuclear factor-κB

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=4143072360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4143072360&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00412.2003

DO - 10.1152/ajpregu.00412.2003

M3 - Article

C2 - 15072965

AN - SCOPUS:4143072360

VL - 287

SP - R592-R599

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 3 56-3

ER -