Mast Cell And Inflammatory Bowel Disease
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 1, 2004; 10(3): 327-331
Published online Feb 1, 2004. doi: 10.3748/wjg.v10.i3.327
Activation of human colon mast cells through proteinase activated receptor-2
Shao-Heng He, Yong-Song He, Hua Xie
Shao-Heng He, Hua Xie, Allergy and Inflammation Research Institute, Shantou University Medical College, Shantou 515031, Guangdong Province, China
Shao-Heng He, Yong-Song He, Immunopharmacology Group, University of Southampton, Southampton, UK
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 30140023, and the Li Ka Shing Foundation, Hong Kong, China, No. C0200001
Correspondence to: Professor Shao-Heng He, Allergy and Inflammation Research Institute, Shantou University Medical College, 22 Xin-Ling Road, Shantou 515031, Guangdong Province, China. shoahenghe@hotmail.com
Telephone: +86-754-8900405 Fax: +86-754-8900192
Received: October 10, 2003
Revised: November 2, 2003
Accepted: November 9, 2003
Published online: February 1, 2004
Abstract

AIM: To investigate the ability of agonists of PAR-2 to stimulate release of tryptase and histamine from human colon mast cells and the potential mechanisms.

METHODS: Enzymatically dispersed cells from human colons were challenged with tc-LIGRLO, tc-OLRGIL, SLIGKV, VKGILS, trypsin, anti-IgE or calcium ionophore A23187, and the cell supernatants after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured using a glass fibre-based fluorometric assay.

RESULTS: Both PAR-2 agonists tc-LIGRLO-NH2 and SLIGKV-NH2 were able to induce dose dependent release of tryptase and histamine from colon mast cells. More than 2.5 fold increase in both tryptase and histamine release was provoked by 100 μmol/mL tc-LIGRLO-NH2, in comparison with only 2.0 fold increase being stimulated by SLIGKV-NH2. The reverse peptides tc-OLRGIL-NH2 and VKGILS-NH2 at the concentrations tested had no effect on the release of these two mediators. The maximum tryptase release elicited by tc-LIGRLO-NH2 was similar to that induced by anti-IgE (10 μg/mL) or calcium ionophore (1 μg/mL), though the latter was a more potent stimulus for histamine release. Both histamine and tryptase release in response to tc-LIGRLO-NH2 were completed within 3 min. Trypsin at concentrations from 1.0 to 100 μg/mL was capable of provoking a dose dependent release of tryptase as well as histamine with a maximum of 16 ng/mL tryptase and 14 ng/mL histamine release being achieved. An approximately 80% and 70% inhibition of trypsin induced release of tryptase and histamine were observed with SBTI, respectively. Pretreatment of cells with metabolic inhibitors or pertussis toxin abolished the actions of tc-LIGRLO-NH2, SLIGKV-NH2 and trypsin.

CONCLUSION: The agonists of PAR-2 and trypsin are potent secretagogues of human colon mast cells, which are likely to contribute to the development of inflammatory disorders in human gut.

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