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Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat
  1. J Santos,
  2. P-C Yang,
  3. J D Söderholm,
  4. M Benjamin,
  5. M H Perdue
  1. Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
  1. M H Perdue, Intestinal Disease Research Program, HSC-3N5C, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada, L8N3Z5.perdue{at}fhs.mcmaster.ca

Abstract

BACKGROUND AND AIMS Stress may be an important factor in exacerbating inflammatory bowel disease but the underlying mechanism is unclear. Defective epithelial barrier function may allow uptake of luminal antigens that stimulate an immune/inflammatory response. Here, we examined the effect of chronic stress on colonic permeability and the participation of mast cells in this response.

METHODS Mast cell deficient Ws/Ws rats and +/+ littermate controls were submitted to water avoidance stress or sham stress (one hour/day) for five days. Colonic epithelial permeability to a model macromolecular antigen, horseradish peroxidase, was measured in Ussing chambers. Epithelial and mast cell morphology was studied by light and electron microscopy.

RESULTS Chronic stress significantly increased macromolecular flux and caused epithelial mitochondrial swelling in +/+ rats, but not in Ws/Ws rats, compared with non-stressed controls. Stress increased the number of mucosal mast cells and the proportion of cells showing signs of activation in +/+ rats. No mast cells or ultrastructural abnormalities of the epithelium were present in Ws/Ws rats. Increased permeability in +/+ rats persisted for 72 hours after stress cessation.

CONCLUSIONS Chronic stress causes an epithelial barrier defect and epithelial mitochondrial damage, in parallel with mucosal mast cell hyperplasia and activation. The study provides further support for an important role for mast cells in stress induced colonic mucosal pathophysiology.

  • epithelial transport
  • mast cells
  • mitochondria
  • psychological stress
  • ultrastructure
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Footnotes

  • Abbreviations used in this paper:
    G
    conductance
    HRP
    horseradish peroxidase
    IBD
    inflammatory bowel disease
    Isc
    short circuit current
    Ws/Ws
    mast cell deficient rats with gene deletion at the “white spotting” (Ws) locus
    +/+
    normal littermates of Ws/Ws rats

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