Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats.
ABSTRACT 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.
- SourceAvailable from: Zhengyuan Xia[show abstract] [hide abstract]
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.PLoS ONE 01/2013; 8(10):e75262. · 3.73 Impact Factor