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Updated: Aug 18, 2026
Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
Stress-induced rat intestinal mast cell intragranular activation and inhibitory effect of sulfated proteoglycans
T C Theoharides1, R Letourneau, P Patra
1Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Insights
Stress impacts the gut lining and mast cells, potentially contributing to cyclic vomiting syndrome. Chondroitin sulfate may help reduce mast cell histamine release, offering a potential therapeutic avenue.
Area of Science:
- Gastroenterology
- Neuroscience
- Immunology
Background:
- Cyclic vomiting syndrome (CVS) is a debilitating condition often linked to migraines and stress.
- Mast cells, implicated in migraines, are located near neurons and activated by neuropeptides.
- Stress is a known trigger for CVS episodes.
Purpose of the Study:
- To investigate the ultrastructural effects of acute stress on rat ileal brush border and mast cells.
- To evaluate the impact of heparin and chondroitin sulfate on mast cell histamine secretion.
Main Methods:
- Acute immobilization stress was applied to rats to induce stress.
- Ultrastructural analysis examined changes in the ileal brush border and mast cells.
- Purified rat peritoneal mast cells were treated with heparin and chondroitin sulfate before stimulation.
Main Results:
- Immobilization stress caused shortening and intercellular gaps in the ileal brush border.
- Stress induced mast cell activation, evidenced by changes in secretory granules, but not typical degranulation.
- Both heparin and chondroitin sulfate significantly reduced histamine release from mast cells.
Conclusions:
- Acute stress alters rat ileal brush border and activates mast cells.
- Chondroitin sulfate demonstrates potential therapeutic value for conditions like CVS by inhibiting mast cell histamine release.
Abstract:
Cyclic vomiting syndrome is characterized by sudden episodes of vomiting and abdominal pain. It occurs primarily in children, is exacerbated by stress, and is often considered a migraine equivalent. Migraines have been linked to mast cells, which are often found close to neurons where they are activated by neuropeptides. We investigated the ultrastructural appearance of rat ileal brush border and mast cells following acute stress by immobilization. The effect of sulfated proteoglycans heparin and chondroitin sulfate was also tested on mast cell histamine secretion. Ileal brush border appeared intact in control animals, but was shorter and exhibited intercellular gaps after 30 min of acute immobilization stress. Mast cell activation in control rats was minimal, while stress induced obvious signs of activation as judged from disappearance of secretory granule electron dense contents. However, these intragranular changes were not accompanied by typical degranulation through exocytosis. Treatment of purified homogeneic rat peritoneal mast cells with 10(-4) M heparin or chondroitin sulfate 30 min prior to stimulation with 0.5 microg/ml compound 48/80 decreased histamine release by over 70% and 50% (P < 0.05), respectively. These results suggest the possible usefulness of chondroitin sulfate in conditions such as cyclic vomiting syndrome.
