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A "CLEAN CASE" OF SYSTEMIC INJURY: MESENTERIC LYMPH AFTER HEMORRHAGIC SHOCK ELICITS A STERILE INFLAMMATORY RESPONSE.

ABSTRACT: Postinjury multiple organ failure results from an inappropriate overwhelming immune response to injury. During trauma and hemorrhagic shock (T/HS), mesenteric ischemia causes gut mucosal breakdown with disruption of the intestinal barrier. It has been proposed that this releases the gut microbiota systemically via postshock mesenteric lymph (PSML), engendering infectious complications. Despite extensive investigation, no clear evidence has been presented for gut bacterial translocation after resuscitation from T/HS. However, such previous studies were limited by available technologies. More sensitive methods, such as quantitative polymerase chain reaction, have since emerged for detection of bacterial presence and danger-associated molecular patterns (DAMPs). Quantitative polymerase chain reaction was applied to PSML derived from a rat model of T/HS. No bacterial presence was detected in a series of 12 samples, whereas multiple lymph samples showed the presence of DAMPs after T/HS. Thus, we confirmed that bacterial translocation does not exist in PSML after resuscitation from T/HS-associated mesenteric ischemia. However, T/HS does increase the presence of mitochondrial DAMPs in PSML. These results support our current position that PSML elaborates remote organ injury by multiple inflammatory mechanisms, including lipid-mediated proinflammatory stimuli, and by contribution from gut-derived DAMPs.

SUBMITTER: Yi J

PROVIDER: S-EPMC4575624 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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A "CLEAN CASE" OF SYSTEMIC INJURY: MESENTERIC LYMPH AFTER HEMORRHAGIC SHOCK ELICITS A STERILE INFLAMMATORY RESPONSE.

Yi Jeniann J Slaughter Anne A Kotter Cassandra V CV Moore Ernest E EE Hauser Carl J CJ Itagaki Kiyoshi K Wohlauer Max M Frank Daniel N DN Silliman Christopher C Banerjee Anirban A Peltz Erik E

Shock (Augusta, Ga.) 20151001 4

Postinjury multiple organ failure results from an inappropriate overwhelming immune response to injury. During trauma and hemorrhagic shock (T/HS), mesenteric ischemia causes gut mucosal breakdown with disruption of the intestinal barrier. It has been proposed that this releases the gut microbiota systemically via postshock mesenteric lymph (PSML), engendering infectious complications. Despite extensive investigation, no clear evidence has been presented for gut bacterial translocation after res ...[more]

PMID: 26196840

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Project description:BackgroundTrauma/hemorrhagic shock (T/HS) causes a release of proinflammatory mediators into the mesenteric lymph (ML) that may trigger a systemic inflammatory response and subsequent organ failure. Recently, we showed that exosomes in postshock ML are biologically active mediators of this inflammation. Because the specific inflammatory mediators in postshock ML exosomes have yet to be characterized, we hypothesized that T/HS would lead to a distinct ML proinflammatory exosome phenotype that could be identified by proteomic analysis. We further hypothesized that their regulation by the neuroenteric axis via the vagus nerve would modify this proinflammatory profile.MethodsMale rats underwent an established T/HS model including 60 minutes of HS followed by resuscitation. Mesenteric lymph was collected before HS (preshock) and after resuscitation (postshock). A subset of animals underwent cervical vagus nerve electrical stimulation (VNS) after the HS phase. Liquid chromatography with tandem mass spectroscopy (LC-MS/MS) followed by protein identification, label free quantification, and bioinformatic analysis was performed on exosomes from the pre-shock and post-shock phases in the T/HS and T/HS + vagus nerve electrical stimulation groups. Biological activity of exosomes was evaluated using a monocyte nuclear factor kappa B (NF-κB) activity assay.ResultsML exosomes express a distinct protein profile after T/HS with enrichment in pathways associated with cell signaling, cell death and survival, and the inflammatory response. Stimulation of the vagus nerve following injury attenuated the transition of ML exosomes to this T/HS-induced inflammatory phenotype with protein expression remaining similar to pre-shock. Monocyte NF-κB activity was increased after exposure to ML exosomes harvested after T/HS, while ML exosomes from preshock had no effect on monocyte NF-κB expression.ConclusionPostshock ML exosomes carry a distinct, proinflammatory protein cargo. Stimulating the vagus nerve prevents the T/HS-induced changes in ML exosome protein payload and suggests a novel mechanism by which the neuroenteric axis may limit the systemic inflammatory response after injury.

Dataset Information

A "CLEAN CASE" OF SYSTEMIC INJURY: MESENTERIC LYMPH AFTER HEMORRHAGIC SHOCK ELICITS A STERILE INFLAMMATORY RESPONSE.

Publications

A "CLEAN CASE" OF SYSTEMIC INJURY: MESENTERIC LYMPH AFTER HEMORRHAGIC SHOCK ELICITS A STERILE INFLAMMATORY RESPONSE.

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