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  • Title: Mast cells trigger epithelial barrier dysfunction, bacterial translocation and postoperative ileus in a mouse model.
    Author: Snoek SA, Dhawan S, van Bree SH, Cailotto C, van Diest SA, Duarte JM, Stanisor OI, Hilbers FW, Nijhuis L, Koeman A, van den Wijngaard RM, Zuurbier CJ, Boeckxstaens GE, de Jonge WJ.
    Journal: Neurogastroenterol Motil; 2012 Feb; 24(2):172-84, e91. PubMed ID: 22122661.
    Abstract:
    BACKGROUND: Abdominal surgery involving bowel manipulation commonly results in inflammation of the bowel wall, which leads to impaired intestinal motility and postoperative ileus (POI). Mast cells have shown to play a key role in the pathogenesis of POI in mouse models and human studies. We studied whether mast cells contribute to the pathogenesis of POI by eliciting intestinal barrier dysfunction. METHODS: C57BL/6 mice, and two mast cell-deficient mutant mice Kit(W/W-v) , and Kit(W-sh/W-sh) underwent laparotomy (L) or manipulation of the small bowel (IM). Postoperative inflammatory infiltrates and cytokine production were assessed. Epithelial barrier function was determined in Ussing chambers, by measuring transport of luminal particles to the vena mesenterica, and by assessing bacterial translocation. KEY RESULTS: In WT mice, IM resulted in pro-inflammatory cytokine and chemokine production, and neutrophil extravasation to the manipulated bowel wall. This response to IM was reduced in mast cell-deficient mice. IM caused epithelial barrier dysfunction in WT mice, but not in the two mast cell-deficient strains. IM resulted in a decrease in mean arterial pressure in both WT and mast cell-deficient mice, indicating that impaired barrier function was not explained by tissue hypoperfusion, but involved mast cell mediators. CONCLUSIONS & INFERENCES: Mast cell activation during abdominal surgery causes epithelial barrier dysfunction and inflammation of the muscularis externa of the bowel. The impairment of the epithelial barrier likely contributes to the pathogenesis of POI. Our data further underscore that mast cells are bona fide cellular targets to ameliorate POI.
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