Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism
- 29 December 2009
- journal article
- research article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 106 (52) , 22381-22386
Abstract
Altered intestinal barrier function is postulated to be a central predisposing factor to intestinal diseases, including inflammatory bowel diseases and food allergies. However, the mechanisms involved in maintaining homeostatic intestinal barrier integrity remain undefined. In this study, we demonstrate that mice deficient in mast cells ( Kit W-sh/W-sh [Wsh]) or mast cell chymase (Mcpt4 −/− ) have significantly decreased basal small intestinal permeability compared with wild-type (WT) mice. Altered intestinal barrier function was linked to decreased intestinal epithelial cell migration along the villus/crypt axis, altered intestinal morphology, and dysregulated claudin-3 crypt expression. Remarkably, engraftment of Wsh mice with WT but not Mcpt4 −/− mast cells restored intestinal epithelial cell migration, morphology, and intestinal epithelial barrier function. Collectively, these findings identify a mechanism by which mast cells regulate homeostatic intestinal epithelial migration and barrier function.Keywords
This publication has 36 references indexed in Scilit:
- IL-9– and mast cell–mediated intestinal permeability predisposes to oral antigen hypersensitivityJournal of Experimental Medicine, 2008
- The extended cleavage specificity of the rodent β-chymases rMCP-1 and mMCP-4 reveal major functional similarities to the human mast cell chymaseMolecular Immunology, 2008
- MUCOSAL MAST CELL PROTEASES ARE INVOLVED IN COLONIC PERMEABILITY ALTERATIONS AND SUBSEQUENT BACTERIAL TRANSLOCATION IN ENDOTOXEMIC RATSShock, 2007
- A Key Role for Mast Cell Chymase in the Activation of Pro-matrix Metalloprotease-9 and Pro-matrix Metalloprotease-2Journal of Biological Chemistry, 2005
- Enteric neuroimmunophysiology and pathophysiology 1,2 1The concepts for enteric neuroimmunophysiology in this article emerged, in part, from collaborative work with Professor Helen J. Cooke and several postdoctoral visitors and students in the author’s laboratories (including Fedias Christofi, Thomas Frieling, Jeffrey M. Palmer, Kenji Tamura, Paul R. Wade, Yu-Z. Wang, Yun Xia, Dimiter Zafirov, Hong-Zhen Hu, and Sumei Liu). 2The author is indebted to Professor Gilbert A. Castro of the University of Texas-Houston Health Science Center for introducing the author to the concept of a common mucosal immune system and for sending Jeffrey M. Palmer to the author for postdoctoral training in the early 1980s.Gastroenterology, 2004
- The Chymase, Mouse Mast Cell Protease 4, Constitutes the Major Chymotrypsin-like Activity in Peritoneum and Ear Tissue. A Role for Mouse Mast Cell Protease 4 in Thrombin Regulation and Fibronectin TurnoverJournal of Experimental Medicine, 2003
- Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence?Gut, 1999
- Mast cells that reside at different locations in the jejunum of mice infected with Trichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype.Journal of Cell Biology, 1996
- Basal secretion and anaphylactic release of rat mast cell protease-II (RMCP-II) from ex vivo perfused rat jejunum: translocation of RMCP-II into the gut lumen and its relation to mucosal histology.Gut, 1995
- Ultrastructural and Immunohistochemical Characterization of Normal Mast Cells at Multiple Body SitesJournal of Investigative Dermatology, 1991