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Development of dextran sulphate sodium-induced experimental colitis is suppressed in genetically mast cell-deficient
1Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Abstract:
Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC). In the present study we investigated the role of intestinal MMC in the development of dextran sulphate sodium (DSS)-induced experimental colitis using Ws/Ws rats. Ws/Ws and control (+/+) rats were given a 3% DSS aqueous solution orally for 10 days, and the subsequent mucosal damage was evaluated macroscopically and histologically. The mucosal myeloperoxidase (MPO) activities and histamine levels were also measured. (i) DSS induced severe oedema and hyperaemia with sporadic erosions in the control (+/+) rats, but these changes were significantly attenuated in the Ws/Ws rats (P < 0.01). (ii) The microscopic mucosal damage score was lower in the Ws/Ws rats than in the control (+/+) rats (P = 0.06). (iii) There were no significant differences in mucosal MPO activity between the Ws/Ws and control (+/+) rats (P = 0.46). (iv) The mucosal histamine levels in the colon were significantly reduced in the Ws/Ws rats compared with the control (+/+) rats (P < 0.05). (v) Significant positive correlations were observed between mucosal histamine levels and the degree of mucosal oedema (calculated as colonic wet weight/protein content) (r = 0.778, P < 0.01), and between histamine levels and the macroscopic damage (r = 0.623, P < 0.05), respectively. (vi) DSS induced a local recruitment of MMC in the colonic mucosa of Ws/Ws rats, and mucosal damage gradually increased in accordance with this MMC recruitment. These results indicate that MMC play an important role in the development of DSS colitis.
Insights
Mucosal-type mast cells (MMC) are crucial in dextran sulphate sodium (DSS)-induced colitis development. Ws/Ws rats, lacking MMC, showed reduced DSS colitis severity, indicating MMC
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Ws/Ws rats possess a c-kit gene deletion, resulting in deficiencies of both mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC).
- Dextran sulphate sodium (DSS)-induced experimental colitis is a widely used model to study inflammatory bowel disease.
Purpose of the Study:
- To investigate the specific role of intestinal mucosal-type mast cells (MMC) in the pathogenesis of DSS-induced experimental colitis.
- To utilize Ws/Ws rats, which are deficient in MMC, as a model to elucidate MMC involvement in colitis.
Main Methods:
- Administration of 3% DSS aqueous solution orally to Ws/Ws rats and control (+/+) rats for 10 days.
- Macroscopic and histological evaluation of mucosal damage.
- Measurement of mucosal myeloperoxidase (MPO) activities and histamine levels in the colon.
Main Results:
- DSS-induced severe edema and hyperemia in control rats were significantly attenuated in Ws/Ws rats.
- Microscopic mucosal damage scores were lower in Ws/Ws rats compared to controls.
- Mucosal histamine levels were significantly reduced in Ws/Ws rats, correlating positively with mucosal edema and macroscopic damage.
- DSS induced local recruitment of MMC in the colonic mucosa of Ws/Ws rats, with increasing mucosal damage correlating with MMC recruitment.
Conclusions:
- Mucosal-type mast cells (MMC) play a significant role in the development and severity of DSS-induced experimental colitis.
- The absence of MMC in Ws/Ws rats confers protection against DSS-induced colitis.
- Histamine levels, modulated by MMC, are closely linked to the degree of mucosal damage in DSS colitis.