TY - JOUR T1 - Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat JF - Gut JO - Gut SP - 630 LP - 636 DO - 10.1136/gut.48.5.630 VL - 48 IS - 5 AU - J Santos AU - P-C Yang AU - J D Söderholm AU - M Benjamin AU - M H Perdue Y1 - 2001/05/01 UR - http://gut.bmj.com/content/48/5/630.abstract N2 - 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.GconductanceHRPhorseradish peroxidaseIBDinflammatory bowel diseaseIscshort circuit currentWs/Wsmast cell deficient rats with gene deletion at the “white spotting” (Ws) locus+/+normal littermates of Ws/Ws rats ER -