Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats

Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Injury (Impact Factor: 2.14). 01/2012; 43(8):1250-6. DOI: 10.1016/j.injury.2011.12.027
Source: PubMed


Small intestinal ischemia-reperfusion (IIR) injury may lead to severe local and remote tissue injury, especially acute lung injury (ALI). Mast cell activation plays an important role in IIR injury. It is unknown whether IIR mediates lung injury via mast cell activation.
Adult SD rats were randomized into sham operated group (S), sole IIR group (IIR) in which rats were subjected to 75 min of superior mesenteric artery occlusion followed by 4h reperfusion, or IIR being respectively treated with the mast cell stabilizer Cromolyn Sodium (IIR+CS group), with the tryptase antagonist Protamine (IIR+P group), with the histamine receptor antagonist Ketotifen (IIR+K group), or with the mast cell degranulator Compound 48/80 (IIR+CP group). The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7(MCP7). Pulmonary mast cell number and levels of histamine, TNF-α and IL-8 were quantified.
IIR resulted in lung injury evidenced as significant increases in lung histological scores (P<0.05 IIR vs. S), accompanied with concomitant increases of mast cell counts and elevations in TNF-α and IL-8 concentrations and reductions in histamine levels (all P<0.05 IIR vs. S). IIR also increased lung tissue tryptase and MCP7 protein expressions (all P<0.05, IIR vs. S). Cromolyn Sodium, Ketotifen and Protamine significantly reduced whilst Compound 48/80 aggravated IIR mediated ALI and the above biochemical changes (P<0.05).
Mast cells activation play a critical role in IIR mediated ALI.

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Available from: Zhengyuan Xia, Jul 15, 2014
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    • "Interestingly, the human lung contains abundant mast cells that exhibit similar subtypes to those in the intestine [for instance, more than 90 % are MCγ subtype (i.e., only tryptase containing)]. Therefore, IFN-γ may easily target , activate mast cells in the lung and then cause the acute lung injury or ARDS [30]. This may partly explain why the lung is the first and most common organ to be injured in MODS. "
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    • "Although mast cells are present in all body tissues, they are mostly observed around the capillaries of the skin and the respiratory system and the vessels of the lymphatic system [8,9]. It has been reported that mast cells play a role in inflammatory and allergic diseases of the respiratory system [10-12]. In ischemic injuries, ALI fundamentally develops through the release of mast-cell-activated cytokines such as histamine and tryptase [12,13]. "
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    • "Until now, the functions of MC are not completely understood. We had shown that MCs were involved in ALI after small intestinal I/R [6], [8]. It is possible that MC activation participates in the process of activating remote organ inflammation. "
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