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

Background and aims-Stress may be an important factor in exacerbating infla mmatory bowel disease but the underlying mechanism is unclear. Defective ep ithelial barrier function may allow uptake of luminal antigens that stimula te 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 sub mitted to water avoidance stress or sham stress (one hour/day) for five day s. Colonic epithelial permeability to a model macromolecular antigen, horse radish peroxidase, was measured in Ussing chambers. Epithelial and mast cel l morphology was studied by light and electron microscopy. Results-Chronic stress significantly increased macromolecular flux and caus ed epithelial mitochondrial swelling in +/+ rats, but not in Ws/Ws rats, co mpared with non-stressed controls. Stress increased the number of mucosal m ast cells and the proportion of cells showing signs of activation in tli ra ts. No mast cells or ultrastructural abnormalities of the epithelium were p resent in Ws/Ws rats. increased permeability in +/+ rats persisted for 72 h ours after stress cessation. Conclusions-Chronic stress causes an epithelial barrier defect and epitheli al mitochondrial damage, in parallel with mucosal mast call hyperplasia and activation. The study provides further support for an important role for m ast cells in stress induced colonic mucosal pathophysiology.