Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat
Open accessAbstract
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.
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Inflammatory intestinal leukocytes, including IL17+ T cells and mast cells, may contribute to breakdown of the intestinal epithelial barrier and downregulation of CLDN5, OCLN, and ZO-2.
“Mechanistically, inflammatory intestinal leukocytes, including IL17+ T cells as well as mast cells, may contribute to the breakdown of the intestinal epithelial barrier and the accompanying downregulation of tight junction proteins CLDN5, occludin (OCLN) and tight junction protein 2 (ZO-2)106,107.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [106]
The Abstract (page not specified) reports that chronic stress impaired the colonic barrier in rats with mast cells but not in mast-cell-deficient rats, supporting a possible mast-cell contribution. The Discussion (page not specified) mentions tight-junction proteins only as part of a proposed mechanism for permeability changes in other models. Our copy does not report IL17+ T-cell involvement or downregulation of CLDN5, OCLN, or ZO-2. (LLM, conf=0.90)
Experimental — accuracy not yet measuredMucosal mast cell degranulation within the gut can affect host intestinal integrity and has been related to visceral pain.
“Mucosal mast cell degranulation within the gut can affect host intestinal integrity (Santos et al., 2001) and has been related to visceral pain (Barbara et al., 2004).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Santos et al., 2001
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- Authors
- Santos, J., Yang, P.-C., Söderholm, J. D., Benjamin, M., & Perdue, M. H.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Perdue, M H
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2001-05-01
- Volume
- 48
- Issue
- 5
- Pages
- 630-636
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1728291
- OpenAlex
- W2141354880
- Cited by
- 313
- References
- 46
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 16 · 2019: 18 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 13 · 2014: 10 · 2013: 16 · 2012: 22
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- mast cells, chronic stress, colonic permeability, inflammatory bowel disease, water avoidance stress, mitochondrial swelling, mast cell activation
- MeSH terms
- Analysis of Variance, Animals, Cell Membrane Permeability, Electric Conductivity, Gastrointestinal Transit, Horseradish Peroxidase, Intestinal Mucosa, Mast Cells, Microscopy, Electron, Mitochondria, Rats, Mutant Strains, Stress, Psychological, Statistics, Nonparametric, Rats
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