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Association of Toll-like receptor signaling and reactive oxygen species: a potential therapeutic target for posttrauma acute lung injury.

Xiang M, Fan J, Fan J - Mediators Inflamm. (2010)

Bottom Line: Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response.Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMvarphi) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator.This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.

ABSTRACT
Acute lung injury (ALI) frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS). Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMvarphi) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

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Related in: MedlinePlus

Model of shock-activated PMN in mediating the TLR4-TLR2 cross talk in AMϕ and AMϕ priming. Hemorrhagic shock-activated PMNs primarily migrate into alveoli in response to a trivial inflammatory stimulus, such as LPS, and interact with AMϕ. The interaction between PMN and AMϕ enhances LPS-induced TLR2 expression (+) in the AMϕ, possibly mediated by PMNs-derived oxidants and augmented NF-κB activation. The increased TLR2 expression results in the amplified response of AMϕ to the TLR2 agonist (PGN), thereby augmenting cytokines and chemokines expression (circled +) and promoting enhanced PMN transalveolar migration. Thus, the shock-activated PMN-mediated TLR4-TLR2 cross talk activates a positive feedback signal leading to AMϕ priming and exaggerated lung inflammation in response to invading pathogens.
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fig2: Model of shock-activated PMN in mediating the TLR4-TLR2 cross talk in AMϕ and AMϕ priming. Hemorrhagic shock-activated PMNs primarily migrate into alveoli in response to a trivial inflammatory stimulus, such as LPS, and interact with AMϕ. The interaction between PMN and AMϕ enhances LPS-induced TLR2 expression (+) in the AMϕ, possibly mediated by PMNs-derived oxidants and augmented NF-κB activation. The increased TLR2 expression results in the amplified response of AMϕ to the TLR2 agonist (PGN), thereby augmenting cytokines and chemokines expression (circled +) and promoting enhanced PMN transalveolar migration. Thus, the shock-activated PMN-mediated TLR4-TLR2 cross talk activates a positive feedback signal leading to AMϕ priming and exaggerated lung inflammation in response to invading pathogens.


Association of Toll-like receptor signaling and reactive oxygen species: a potential therapeutic target for posttrauma acute lung injury.

Xiang M, Fan J, Fan J - Mediators Inflamm. (2010)

Model of shock-activated PMN in mediating the TLR4-TLR2 cross talk in AMϕ and AMϕ priming. Hemorrhagic shock-activated PMNs primarily migrate into alveoli in response to a trivial inflammatory stimulus, such as LPS, and interact with AMϕ. The interaction between PMN and AMϕ enhances LPS-induced TLR2 expression (+) in the AMϕ, possibly mediated by PMNs-derived oxidants and augmented NF-κB activation. The increased TLR2 expression results in the amplified response of AMϕ to the TLR2 agonist (PGN), thereby augmenting cytokines and chemokines expression (circled +) and promoting enhanced PMN transalveolar migration. Thus, the shock-activated PMN-mediated TLR4-TLR2 cross talk activates a positive feedback signal leading to AMϕ priming and exaggerated lung inflammation in response to invading pathogens.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2913855&req=5

fig2: Model of shock-activated PMN in mediating the TLR4-TLR2 cross talk in AMϕ and AMϕ priming. Hemorrhagic shock-activated PMNs primarily migrate into alveoli in response to a trivial inflammatory stimulus, such as LPS, and interact with AMϕ. The interaction between PMN and AMϕ enhances LPS-induced TLR2 expression (+) in the AMϕ, possibly mediated by PMNs-derived oxidants and augmented NF-κB activation. The increased TLR2 expression results in the amplified response of AMϕ to the TLR2 agonist (PGN), thereby augmenting cytokines and chemokines expression (circled +) and promoting enhanced PMN transalveolar migration. Thus, the shock-activated PMN-mediated TLR4-TLR2 cross talk activates a positive feedback signal leading to AMϕ priming and exaggerated lung inflammation in response to invading pathogens.
Bottom Line: Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response.Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMvarphi) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator.This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.

ABSTRACT
Acute lung injury (ALI) frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS). Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMvarphi) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

Show MeSH
Related in: MedlinePlus