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Mast Cells Regulate Homeostatic Intestinal Epithelial Migration And Barrier Function By A Chymase/Mcpt4-dependent Mechanism
K. Groschwitz, R. Ahrens, Heather Osterfeld, M. Gurish, X. Han, M. Åbrink, F. Finkelman, G. Pejler, S. Hogan
Published 2009 · Biology, Medicine
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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 (KitW-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.
This paper references
Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence?
J. Söderholm (1999)
Ultrastructural identification of human mast cells resembling skin mast cells stimulated to develop in long‐term human cord blood mononuclear cells cultured with 3T3 murine skin fibroblasts
Ann M. Dvorak (1992)
MUCOSAL MAST CELL PROTEASES ARE INVOLVED IN COLONIC PERMEABILITY ALTERATIONS AND SUBSEQUENT BACTERIAL TRANSLOCATION IN ENDOTOXEMIC RATS
R. Moriez (2007)
Tissue‐specific expression of mast cell granule serine proteinases and their role in inflammation in the lung and gut
H. Miller (2002)
Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine.
C. Gao (2002)
Ultrastructural and immunohistochemical characterization of normal mast cells at multiple body sites.
N. Weidner (1991)
and their relatives
J Wyatt (1993)
Intestinal permeability in patients with adverse reactions to food.
M. T. Ventura (2006)
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.
C. Scudamore (1995)
Zonulin Upregulation Is Associated With Increased Gut Permeability in Subjects With Type 1 Diabetes and Their Relatives
A. Sapone (2006)
Rodent alpha-chymases are elastase-like proteases.
Y. Kunori (2002)
IL-9– and mast cell–mediated intestinal permeability predisposes to oral antigen hypersensitivity
E. Forbes (2008)
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 Turnover
E. Tchougounova (2003)
Mast Cell Chymase Decreases the Barrier Function and Inhibits the Migration of Corneal Epithelial Cells
N. Ebihara (2005)
Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity.
R. Agarwal (2005)
Constitutive expression of mouse mast cell protease‐1 in normal BALB/c mice and its up‐regulation during intestinal nematode infection
J. Wastling (1997)
Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation.
M. Perdue (1991)
Mast cells disrupt epithelial barrier function during enteric nematode infection
J. McDermott (2003)
Intestinal barrier function: molecular regulation and disease pathogenesis.
Katherine R. Groschwitz (2009)
A Key Role for Mast Cell Chymase in the Activation of Pro-matrix Metalloprotease-9 and Pro-matrix Metalloprotease-2*
E. Tchougounova (2005)
Effect of mesenteric ischemia and reperfusion or hemorrhagic shock on intestinal mucosal permeability and ATP content in rats.
S. Wattanasirichaigoon (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
D. Friend (1996)
2-(8-Hydroxy-6-Methoxy-1-Oxo-1H-2-Benzopyran-3-yl) Propionic Acid, an Inhibitor of Angiogenesis, Ameliorates Renal Alterations in Obese Type 2 Diabetic Mice
K. Ichinose (2006)
Immunohistochemical study of chymase-positive mast cells in inflammatory bowel disease.
A. Andoh (2006)
Mast cell proteases.
R. Woodbury (1981)
Delayed Expulsion of the Nematode Trichinella spiralisIn Mice Lacking the Mucosal Mast Cell–Specific Granule Chymase, Mouse Mast Cell Protease-1
P. Knight (2000)
Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.
R. V. van Elburg (1993)
Chymase increases glomerular albumin permeability via protease-activated receptor-2
R. Sharma (2006)
Rapid lineage-specific diversification of the mast cell chymase locus during mammalian evolution
Maike Gallwitz (2006)
Intestinal permeability and the prediction of relapse in Crohri's disease
J. Wyatt (1993)
Granule proteinases define mast cell heterogeneity in the serosa and the gastrointestinal mucosa of the mouse.
H. Miller (1988)
Development of multiple food allergies in children taking tacrolimus after heart and liver transplantation
Ö. Özdemir (2006)
Enteric neuroimmunophysiology and pathophysiology.
J. Wood (2004)
The extended cleavage specificity of the rodent beta-chymases rMCP-1 and mMCP-4 reveal major functional similarities to the human mast cell chymase.
M. Andersson (2008)
Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation
J. Berkes (2003)
Physiological and pathophysiological functions of intestinal mast cells
S. Bischoff (2009)
Clustering of increased small intestinal permeability in families with Crohn's disease.
M. Peeters (1997)
Rodent α‐chymases are elastase‐like proteases
Y. Kunori (2002)
This paper is referenced by
The Mucosal Immune System and Gastrointestinal Inflammation
F. Cominelli (2009)
The emerging role of mast cell proteases in asthma
G. Pejler (2019)
New era for mucosal mast cells: their roles in inflammation, allergic immune responses and adjuvant development
Y. Kurashima (2014)
Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung.
Ismé M. de Kleer (2016)
1 Mucosal Expression of Claudins in Celiac Disease
Dorottya Nagy-Szakál (2017)
Food-induced anaphylaxis: mast cells as modulators of anaphylactic severity
S. Hogan (2012)
Mast cell activation disease and the modern epidemic of chronic inflammatory disease.
L. Afrin (2016)
This information is current as Complex-Mediated Glomerulonephritis Inflammation and Fibrosis in Immune Renal Function by Contributing to Mouse Mast Cell Protease-4 Deteriorates
L. Scandiuzzi (2010)
Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?
S. Heuston (2012)
Mast cells and IgE activation do not alter the development of oral tolerance in a murine model.
M. C. Tunis (2012)
Leukotriene C4 increases the susceptibility of adult mice to Shiga toxin-producing Escherichia coli infection.
G. Cabrera (2015)
Glutamine and intestinal barrier function
B. Wang (2014)
Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors
G. Pejler (2020)
MicroRNAs: New therapeutic targets for intestinal barrier dysfunction.
L. Zhang (2014)
Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/Wv mice
J. Winston (2014)
Innate Immune Cells: Key Regulators of Homeostasis and Inflammation in Gut and Airway Mucosae
Elfi Töpfer (2014)
Ingested allergens must be absorbed systemically to induce systemic anaphylaxis.
R. Strait (2011)
Investigating Molecular Mechanisms Of Mast Cell Migration And Dynamic Interactions With Intestinal Epithelium
Jinmin Lee (2012)
Role of Mast Cells in Inflammatory Bowel Disease and Inflammation-Associated Colorectal Neoplasia in IL-10-Deficient Mice
M. Chichlowski (2010)
Quercetin protects jejunal mucosa from experimental intestinal ischemia reperfusion injury by activation of CD68 positive cells.
Kristína Čurgali (2018)
Structural and functional role of CADM1 on mast cell-neuron cross-talk
Rania Magadmi (2016)
Potential effector and immunoregulatory functions of mast cells in mucosal immunity
L. Reber (2015)
Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats
Yong Li (2019)
Protease phenotype of constitutive connective tissue and of induced mucosal mast cells in mice is regulated by the tissue
Wei Xing (2011)
Pivotal Role of Mouse Mast Cell Protease 4 in the Conversion and Pressor Properties of Big-Endothelin-1
M. Houde (2013)
Intestinal CRF Receptor Subtypes Mediate Divergent Roles in Stress-Induced Intestinal Epithelial Barrier Dysfunction.
Elizabeth L. Overman (2011)
Mast cell proteases: multifaceted regulators of inflammatory disease.
G. Pejler (2010)
Mast Cells, Basophils and Mucosal Immunity
H. Vliagoftis (2015)
Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse
Amber R. Philp (2018)
CRF Induces Intestinal Epithelial Barrier Injury via the Release of Mast Cell Proteases and TNF-α
Elizabeth L. Overman (2012)
The two faces of mast cells in food allergy and allergic asthma: the possible concept of Yin Yang.
A. Kraneveld (2012)
Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis
Chuan-Hui Kuo (2017)See more