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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    ABSTRACT: Our previous study found that somatostatin (SST) inhibited the intestinal inflammatory injury in a macaque model of intestinal ischemia-reperfusion (IIR); however, the underlying mechanism was unclear. The present study was aimed to investigate the effects of SST on IFN-γ and the systemic inflammatory response after IIR. Fifteen macaques were randomly divided into controls, IIR and SST+ IIR groups. ELISA was performed to measure IFN-γ in ileum tissues, ileac epithelial cells (IECs) and ileal lymphocytes, as well as the systemic levels of IL-6, IL-1β, TNF-α and IFN-γ in the peripheral circulation and the portal vein. HE staining was performed to evaluate morphological changes in vital organs. Immunohistochemistry was performed to identify the distribution of IFN-γ, CD4, CD8 and CD57 in the ileum. After IIR, IFN-γ level was significantly increased in the IECs. IL-6, IL-1β and TNF-α were significantly increased in both the portal vein and the peripheral circulation; in contrast, IFN-γ level was increased in the portal vein alone. Prophylactic SST reversed the change in IFN-γ in the IECs and portal vein. SST led to an alleviation of the pathological changes in systemic vital organs. The distribution of CD4(+), CD57(+) and CD8(+) cells was not positively correlated with the secretion of IFN-γ. IECs are the main source of IFN-γ production after IIR. SST may indirectly lead to mast cell deactivation through the inhibition of IFN-γ production by IECs. Pretreatment with SST may be beneficial for preventing a massive systemic inflammatory response in vital organs after IIR.
    Preview · Article · May 2014 · Digestive Diseases and Sciences
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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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    ABSTRACT: Acute pancreatitis is a life-threatening necroinflammatory disease that is characterized by systemic inflammatory response syndrome and acute lung injury even in its very first days. Erythropoietin (EPO) is a hormone considered as an antiapoptotic and cytoprotective with observed receptors of anti-inflammatory effect on organs apart from the liver and the kidneys. In this study, the effects of EPO on pulmonary mast cells and on secondary injury caused by acute pancreatitis are investigated. Twenty one Wistar Albino rats were divided into three groups--sham, control, and EPO groups--with 7 rats per group. Pancreatitis was induced by administering 4.5% sodium taurocholate into the pancreatic duct. A 1000 U/kg/day dosage (three times) of EPO was administered to the EPO group. Blood urea nitrogen (BUN), creatinine, amylase, and troponin I in the serum were studied; and lung, kidney, brain, and heart tissues were examined histopathologically. There were no histopathological changes in the other organ tissues except for the lung tissue. Compared to the control group, the EPO group showed significantly reduced alveolar hemorrhage, septal neutrophil infiltration, lung wall thickness score, and mast cell count in the lung tissue. Administration of EPO reduces the mast cell count and lung wall thickness, and it reduces the alveolar hemorrhage and septal infiltration induced by acute pancreatitis.
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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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    ABSTRACT: Acute lung injury (ALI) is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT) and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB) p65 translocation was assessed by Western blot. The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.
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