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Updated: Jun 5, 2026
09:07
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Essential role for mast cell tryptase in acute experimental colitis
Matthew J Hamilton1, Mark J Sinnamon, Gregory D Lyng
1Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. mjhamilton@partners.org
Summary
Mouse mast cell protease-6 (mMCP-6) significantly worsens experimental colitis. Null mice lacking mMCP-6 show reduced inflammation and weight loss, indicating mMCP-6 is a key mediator in inflammatory bowel disease (IBD) development.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Patients with inflammatory bowel disease (IBD) exhibit elevated human tryptase-beta (hTryptase-β)-positive mast cells (MCs) in the gut.
- Mouse mast cell protease-6 (mMCP-6) shares sequence similarity with hTryptase-β, suggesting a potential role in inflammation.
Purpose of the Study:
- To investigate the role of mMCP-6 and mMCP-7 in experimental colitis models.
- To determine if mMCP-6 or mMCP-7 mediate the inflammatory response in dextran sodium sulfate (DSS) and trinitrobenzene sulfonic acid (TNBS) induced colitis.
Main Methods:
- Comparison of C57BL/6 (B6) mouse lines with differing mMCP-6 and mMCP-7 expression in DSS and TNBS colitis models.
- Assessment of weight loss, colon histopathology, and endoscopic scores.
- Microarray analysis followed by real-time PCR, ELISA, and immunohistochemistry for cytokines, chemokines, and matrix metalloproteinases (MMPs).
Main Results:
- Mice lacking mMCP-6 (mMCP-6-null) exhibited significantly reduced weight loss, colon pathology, and endoscopic scores in DSS-induced colitis compared to wild-type (WT) mice.
- This protective effect of mMCP-6 deficiency was confirmed in TNBS-treated mice.
- DSS-treated WT mice showed increased proinflammatory cytokines, neutrophil-attracting chemokines, and ECM-remodeling MMPs compared to untreated WT and DSS-treated mMCP-6-null mice.
Conclusions:
- mMCP-6, but not mMCP-7, is a critical mast cell-specific mediator in chemically induced colitis.
- This tryptase acts upstream of key factors implicated in the pathogenesis of inflammatory bowel disease (IBD).
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