Cited by 313Gastrointestinal motility and disordersMast cells and histamineInflammatory Bowel Disease

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

Open access
Santos, J, Yang, P-C, Söderholm, J D, Benjamin, M, Perdue, M H·2001·Gut

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/gut.48.5.630

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 measured
  • Mucosal 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

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 46 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

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
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review