Group VIB Ca2+-independent phospholipase A2γ is associated with acute lung injury following trauma and hemorrhagic shock

Aiboshi, Junichi; Kobayashi, Tetsuyuki; Yokoyama, Yuri; Mikami, Saori; Kumagai, Jiro; Onisawa, Keiko; Otomo, Yasuhiro

doi:10.1097/ta.0b013e3182a924f2

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…Studies have shown that the biologic activity of the ML is directly correlated with the inflammatory response of immune cells that lead to remote organ injury, such as ALI (5,6). Moore et al and others have demonstrated that the lipid fraction extracted from postshock ML activates systemic neutrophils, increases endothelial cell permeability, and contributes to lung injury after T/HS (4,7,8). On the other hand, D'Alessandro et al (9) have demonstrated that the protein fraction of ML is not only altered by T/HS but also has the ability to activate neutrophils, suggesting that the protein component may also contribute to the postshock SIRS pathophysiology.…”

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Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

et al. 2017

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Acute lung injury (ALI) is a common cause of morbidity in patients after severe injury due to dysregulated inflammation, which is believed to be driven by gut-derived inflammatory mediators carried mesenteric lymph (ML). We have previously demonstrated that nano-sized extracellular vesicles, called exosomes, secreted into ML after trauma/hemorrhagic shock (T/HS) have the potential to activate immune cells Here, we assess the function of ML exosomes in the development of T/HS-induced ALI and the role of TLR4 in the ML exosome-mediated inflammatory response. ML exosomes isolated from rats subjected to T/HS stimulated NF-κB activation and caused proinflammatory cytokine production in alveolar macrophages. experiments revealed that intravenous injection of exosomes harvested after T/HS, but not before shock, caused recruitment of inflammatory cells in the lung, increased vascular permeability, and induced histologic ALI in naive mice. The exosome-depleted supernatant of ML had no effect on and inflammatory responses. We also demonstrated that both pharmacologic inhibition and genetic knockout of TLR4 completely abolished ML exosome-induced cytokine production in macrophages. Thus, our findings define the critical role of exosomes secreted into ML as a critical mediator of T/HS-induced ALI through macrophage TLR4 activation.-Kojima, M., Gimenes-Junior, J. A., Chan, T. W., Eliceiri, B. P., Baird, A., Costantini, T. W., Coimbra, R. Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation Toll-like receptor 4.

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Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

et al. 2017

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“…Therefore, we determined the minimum sample size (n = 3) according to our prior studies that evaluated the concentration of arachidonic acids in the ML in an intestinal ischemia-reperfusion model. 13,16 Although rats dying during the experiments were planned to be excluded from the analysis, all three rats survived until the end of the experiments and were analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…The effect size could not be estimated before the experiments because we did not have data demonstrating the concentration of lipid metabolites derived from gut microbiota in the ML. Therefore, we determined the minimum sample size (n = 3) according to our prior studies that evaluated the concentration of arachidonic acids in the ML in an intestinal ischemia-reperfusion model 13,16 . Although rats dying during the experiments were planned to be excluded from the analysis, all three rats survived until the end of the experiments and were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Analysis of lipid metabolites derived from gut microbiota in ischemia-reperfusion model

Nakatsutsumi,

Morishita,

Costantini

et al. 2023

J Trauma Acute Care Surg

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Background Disruption of intestinal barrier caused by intestinal ischemia due to hemorrhagic shock, is associated with the pathogenesis of multiple organ dysfunction (MOD) after severe trauma. Mesenteric lymph (ML) plays an important role as a route for transporting inflammatory mediators, including lipids. Post-biotics, such as 10-hydroxy-cis-12-octadecenoic acid (HYA), have received much attention as a treatment option. However, the relationship between post-biotics and MOD has yet to be clarified. The aim of the present study is to analyze lipid metabolites derived from gut microbiota in the intestinal ischemia/reperfusion (IR) rat model. Methods Male Sprague-Dawley rats underwent laparotomy, and their mesenteric lymph duct and superior mesenteric artery (SMA) were exposed. The SMA was clamped for 60 minutes, followed by 120 minutes of reperfusion. The ML and the plasma were collected before and after intestinal IR. Lipids were extracted from plasma and ML, and liquid chromatography-tandem mass spectrometry was performed. Results The concentration of linoleic acid in plasma samples was not different before and after IR; however, the linoleic acid concentration in the ML samples increased after intestinal IR. Eicosapentaenoic acids and docosahexaenoic related to linoleic acids, showed similar changes with IR-induced increase in the ML. The concentration of HYA, a linoleic acid-derived bioactive metabolite produced by gut bacteria, was high in ML samples while that in plasma samples was low. The relative increase rate of HYA in ML samples after IR was higher than that of the plasma samples (the ML samples: relative increase 3.23 ± 1.36, the plasma samples: relative increase 0.95 ± 0.35, n = 3, p = 0.048) Conclusions The present study demonstrated increased linoleic acids and high concentrations of HYA, lipid metabolites derived from gut bacteria in the ML after intestinal lIR. These findings may contribute to clarifying the relation between gut microbiota and MOD after severe trauma. This is a Basic Science paper and, therefore, does not require a level of evidence.

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“…To ensure the reliability of the results, we performed a power analysis before conducting all the experimental work according to the methods used in one of our previous studies. 15 In this past study, we evaluated AA in the ML before and after I/R using mass spectrometry. The AAvalue increased 2.55 times with an SD of approximately 0.26.…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury

Nakatsutsumi

Yagi

Doki

et al. 2021

J Trauma Acute Care Surg

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BACKGROUND: Inflammatory lipid mediators in mesenteric lymph (ML), including arachidonic acid (AA), are considered to play an important role in the pathogenesis of multiple-organ dysfunction after hemorrhagic shock. A previous study suggested that vagus nerve stimulation (VNS) could relieve shock-induced gut injury and abrogate ML toxicity, resulting in the prevention of multiple-organ dysfunction. However, the detailed mechanism of VNS in lymph toxicity remains unclear. The study aimed to investigate the relationship between VNS and inflammatory lipid mediators in ML. METHODS:Male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery obstruction (SMAO) for 60 minutes to induce intestinal ischemia followed by reperfusion and observation. The ML duct was cannulated, and ML samples were obtained both before and after SMAO. The distal ileum was removed at the end of the observation period. In one group of animals, VNS was performed from 10 minutes before 10 minutes after SMAO (5 V, 0.5 Hz). Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of AA was performed for each ML sample. The biological activity of ML was examined using a monocyte nuclear factor κ-light-chainenhancer of activated B cells activation assay. Western blotting of phospholipase A 2 group IIA (PLA 2 -IIA) was also performed for ML and ileum samples. RESULTS:Vagus nerve stimulation relieved the SMAO-induced histological gut injury. The concentration of AA and level of nuclear factor κ-lightchain-enhancer of activated B cells activation in ML increased significantly after SMAO, whereas VNS prevented these responses. Western blotting showed PLA 2 -IIA expression in the ML and ileum after SMAO; however, the appearance of PLA2-IIA band was remarkably decreased in the samples from VNS-treated animals. CONCLUSION: The results suggested that VNS could relieve gut injury induced by SMAO and decrease the production of AA in ML by altering PLA 2 -IIA expression in the gut and ML.

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Group VIB Ca2+-independent phospholipase A2γ is associated with acute lung injury following trauma and hemorrhagic shock

Abstract: The iPLA(2γ) enzyme is possibly involved in the pathogenesis of ALI following T/HS through the mesenteric lymph pathway.

Cited by 8 publications

References 36 publications

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

Analysis of lipid metabolites derived from gut microbiota in ischemia-reperfusion model

Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury

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