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Mast Cells Regulation of Homeostatic Intestinal Barrier Function is dependent on the Human Chymase Homologue, mcpt4.
Author(s) -
Hogan Simon Patrick,
Ahrens Richard,
Osterfeld Heather,
Rothenberg Marc Elliot,
Finkelman Fred,
Abrink Magnus,
Pejler Gunnar,
Groschwitz Katherine
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.121.4
Subject(s) - paracellular transport , barrier function , homeostasis , transcellular , chemistry , tight junction , intestinal permeability , intestinal epithelium , intestinal mucosa , mast cell , medicine , endocrinology , microbiology and biotechnology , epithelium , immunology , biology , permeability (electromagnetism) , biochemistry , genetics , membrane
Disruption of the intestinal epithelial barrier has been proposed to be a central predisposing factor to intestinal diseases, however the molecular mechanisms involved in the maintenance of homeostatic intestinal epithelial barrier integrity has not been defined. We demonstrate a decrease in paracellular and transcellular intestinal permeability in mast cell (MC)‐deficient Kit W‐sh/W‐sh mice as compared to C57Bl/6 WT mice (paracellular [Dextran‐FITC]: 172.3 ± 35.3 vs 378.1 ± 54.3 ng/ml; p < 0.005; transcellular [HRP]: 0.0079 ± 0.0036 vs 1.1129 ± 0.4798 ng/ml; p < 0.05). We confirm MC involvement in homeostatic intestinal barrier function as reconstitution of bone marrow derived mast cells (BMMC's) into Kit W‐sh/W‐sh mice restored intestinal epithelial barrier integrity. Importantly, we identified that MC‐regulation of homeostatic intestinal barrier function was dependent on MC protease 4 ( mcpt4) . Moreover, mcpt‐4 −/− mice intestinal epithelial barrier integrity was decreased as compared to WT mice ([Dextran‐FITC]: 115.3 ± 25.2 vs 378.1 ± 54.3 ng/ml; p < 0.005; [HRP]: 0.179 ± 0.1306 vs 1.1129 ± 0.4798 ng/ml; p < 0.05), to levels equivalent to that of Kit W‐sh/W‐sh mice. Furthermore, reconstitution of mcpt4 −/− BMMC's into Kit W‐sh/W‐sh mice did not restore intestinal epithelial barrier integrity. Collectively, our data demonstrates a critical role for MC's in the regulation of homeostatic intestinal barrier function.