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Gut. 2001 May; 48(5): 630–636.
PMCID: PMC1728291

Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat

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.


Keywords: epithelial transport; mast cells; mitochondria; psychological stress; ultrastructure

Figure 1
Effect of chronic stress on colonic physiology and macromolecule permeability. Mast cell deficient rats (Ws/Ws) and their normal mast cell containing littermates (+/+) were submitted to sham stress or water avoidance stress for five consecutive days. ...
Figure 2
Effect of chronic stress on horseradish peroxidase (HRP) transport and epithelial mitochondria. Mast cell deficient rats (Ws/Ws; left) and their normal mast cell containing littermates (+/+; right) were submitted to water avoidance stress (top photomicrographs) ...
Figure 3
Effect of chronic stress on mast cells in +/+ rats. (A) A non-activated mast cell (MC) in the mucosa of a sham stressed +/+ rat showing numerous homogeneous electron dense granules. (B) A mast cell (MC) with piecemeal-type degranulation. The mast cell ...

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