Gastroenterology

Gastroenterology

Volume 123, Issue 4, October 2002, Pages 1099-1108
Gastroenterology

Basic–Alimentary Tract
Chronic stress induces mast cell–dependent bacterial adherence and initiates mucosal inflammation in rat intestine,☆☆,,★★,,♢♢

https://doi.org/10.1053/gast.2002.36019Get rights and content

Abstract

Background & Aims: Chronic psychological stress is an important factor in relapses of intestinal disorders, but it remains unclear if stress can induce primary gut inflammation in a previously healthy host. Methods: Mast cell-deficient (Ws/Ws) rats and wild-type control (+/+) rats were submitted to water avoidance stress or sham stress (1 h/day) for 10 consecutive days, as a model of ongoing life stress. Results: Both rat groups had similar systemic responses to stress, as assessed by changes in weight, corticosterone levels, and defecation. In +/+ rats, chronic stress induced barrier dysfunction in the ileum and colon (increased macromolecular permeability and depletion of mucus) and ultrastructural changes in epithelial cells (enlarged mitochondria and presence of autophagosomes) associated with bacterial adhesion and penetration into enterocytes. Moreover, hyperplasia and activation of mast cells, infiltration of neutrophils and mononuclear cells, and increased myeloperoxidase (MPO) activity were documented in the mucosa. In intestine of Ws/Ws rats, epithelial function and morphology were unchanged by chronic stress, bacterial-epithelial cell interaction was not demonstrated, and there was no evidence of inflammatory cell infiltration. Conclusions: These findings suggest that chronic psychological stress can be an initiating factor in intestinal inflammation by impairing mucosal defenses against luminal bacteria and highlight the importance of mast cells in this process.

GASTROENTEROLOGY 2002;123:1099-1108

Section snippets

Animals

Mast cell-deficient Ws/Ws rats and their +/+ littermate controls were obtained from a breeding colony at McMaster University, as in previous studies12, 13, 14, 15 The original breeders were obtained from Dr. Y. Kitamura, Osaka, Japan, who identified a spontaneous mutation (Ws/+) in a BN/fMai rat colony, and the heterozygotes rats were bred with female rats of the Donryu strain to obtain viable Ws/Ws rats. Ws/Ws rats have a 12-base deletion in the tyrosine kinase domain of the c-kit gene, and,

Chronic stress induces systemic changes in both +/+ and Ws/Ws rats

Animal weight remained relatively constant or decreased slightly in rats exposed to WAS (Figure 1A).

. Effects of chronic stress on rat weight and defecation. Mast cell-deficient Ws/Ws rats (triangles) and their normal +/+ littermates (rectangles) were submitted to sham stress (open symbols) or water avoidance stress (filled symbols) 1 hour/day on 10 consecutive days. (A) Change in body weight expressed as percentage of body weight on day 1, during the 10-day study period. (B) Fecal pellet

Discussion

The novel findings from this study indicate that chronic psychological stress can alter host defense to enteric bacteria and initiate mucosal inflammation. In addition, a comparison of the results in Ws/Ws and +/+ rats suggests that mast cells play an important role in the stress-induced mucosal changes. From previous studies, we know that mucosal permeability is increased up to 24 hours after acute stress11 and 3 days after a 5-day chronic stress period.12, 13 In the present study, mucosal

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      For instance, signs of colonic and jejunal inflammation have been reported in rats subjected to 14-day crowding-induced chronic stress, associated with a 3.5-fold increase in circulating corticosterone (and a yet higher peak at stress onset) and activation of mast cells [93,94]. Continued (10 d) water avoidance stress in rats results in increased colonic myeloperoxidase activity and leukocyte infiltration, associated with hypercorticosteronemia (∼2-fold, 17-fold in the first hour), mucus depletion, and permeability defects [95]. Small intestinal inflammation is induced by 3-week cold exposure stress in rats (with severely depressed epithelial proliferation rate) [96] and by 4-week environmental factors stress [97].

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    Address requests for reprints to: Mary H. Perdue, Prof., Intestinal Disease Research Program, HSC-3N5C, McMaster University, 1200 Main St. West, Hamilton, Ontario L8N3Z5, Canada.

    ☆☆

    Supported by grants from the Canadian Institutes for Health Research, the Swedish Medical Research Council, and AstraZeneca R&D, Molndal, Sweden.

    J. Söderholm (recently returned to the Department of Biomedicine and Surgery, Linkoping, Sweden) was the recipient of a Postdoctoral Fellowship from the Canadian Institutes for Health Research.

    ★★

    P. Ceponis was the recipient of an Ontario Graduate Studentship Award.

    A. Vohra was the recipient of a Summer Studentship from the Canadian association of Gastroenterology.

    ♢♢

    P. Sherman holds a Canada Research Chair in Gastrointestinal Disease.

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