Mast cells trigger epithelial barrier dysfunction, bacterial translocation and postoperative ileus in a mouse model
Article first published online: 29 NOV 2011
© 2011 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 24, Issue 2, pages 172–e91, February 2012
How to Cite
Snoek, S. A., Dhawan, S., van Bree, S. H., Cailotto, C., van Diest, S. A., Duarte, J. M., Stanisor, O. I., Hilbers, F. W., Nijhuis, L., Koeman, A., van den Wijngaard, R. M., Zuurbier, C. J., Boeckxstaens, G. E. and de Jonge, W. J. (2012), Mast cells trigger epithelial barrier dysfunction, bacterial translocation and postoperative ileus in a mouse model. Neurogastroenterology & Motility, 24: 172–e91. doi: 10.1111/j.1365-2982.2011.01820.x
- Issue published online: 16 JAN 2012
- Article first published online: 29 NOV 2011
- Received: 27 May 2011 Accepted for publication: 22 October 2011
- barrier function;
- mast cells;
- postoperative ileus
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 KitW/W-v, and KitW-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.