Release of Mast Cell Tryptase from Human Colorectal Mucosa in Inflammatory Bowel Disease

Raithel, Martin; Winterkamp, Sandra; Pacurar, A; Ulrich, P.; Hochberger, J; Hahn, Eckhart G.

doi:10.1080/003655201750065933

Cited by 127 publications

(67 citation statements)

References 25 publications

(45 reference statements)

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“…The presence of increased numbers of mast cells and its mediators can be found in the mucosa of patients with IBD (13,27). Because the gastrointestinal tract is exposed to exogenous agents entering the body by intestinal bacteria and via food intake, a constant activation of the immune system occurs.…”

Section: Discussionmentioning

confidence: 99%

“…4. Also the number of CAE-positive mast cells was increased after DNFB sensitization and DNS challenge compared with vehiclesensitized and DNS-challenged mice (mast cell number per colon: vehicle/DNS 16 (6 -22), DNFB/DNS 28 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36); results are expressed as median (range); p Ͻ 0.05, n ϭ 6). TNF-␣ is one of the major cytokines released upon mast cell activation.…”

Section: Dnfb-induced Hypersensitivity Is Associated With Mast Cell Amentioning

confidence: 99%

See 1 more Smart Citation

Critical Role for Mast Cells in the Pathogenesis of 2,4-Dinitrobenzene-Induced Murine Colonic Hypersensitivity Reaction

Rijnierse

Koster

Nijkamp

et al. 2006

The Journal of Immunology

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The immunological mechanisms underlying the role of mast cells in the pathogenesis of inflammatory bowel disease (IBD) are poorly defined. In this study, non-IgE mediated colonic hypersensitivity responses in BALB/c mice induced by skin sensitization with dinitrofluorobenzene (DNFB) followed by an intrarectal challenge with dinitrobenzene sulfonic acid featured as a model to study the role of mast cells in the development of IBD. Vehicle- or DNFB-sensitized mice were monitored for clinical symptoms and inflammation 72 h after dinitrobenzene sulfonic acid challenge. DNFB-sensitized mice developed diarrheic stool, increased colonic vascular permeability, hypertrophy of colonic lymphoid follicles (colonic patches), and showed cellular infiltration at the microscopic level. Increased numbers of mast cells were found in the colon of DNFB-sensitized mice located in and around colonic patches associated with elevated levels of mouse mast cell protease-1 in plasma indicating mast cell activation. Colonic patches of DNFB mice, stimulated in vitro with stem cell factor indicated that an increase in TNF-α levels in the colon is mainly mast cell originated. Finally, neutrophil infiltration was observed in the colon of DNFB-sensitized mice. Induction of this model in mast cell-deficient WBB6F1 W/Wv mice shows a profound reduction of characteristics of the colonic hypersensitivity reaction. Reconstitution with bone marrow-derived mast cells in WBB6F1 W/Wv mice fully restored the inflammatory response. This study demonstrates the importance of mast cells in the development of clinical symptoms and inflammation in the presented murine model for IBD.

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Section: Discussionmentioning

confidence: 99%

Section: Dnfb-induced Hypersensitivity Is Associated With Mast Cell Amentioning

confidence: 99%

Critical Role for Mast Cells in the Pathogenesis of 2,4-Dinitrobenzene-Induced Murine Colonic Hypersensitivity Reaction

Rijnierse

Koster

Nijkamp

et al. 2006

The Journal of Immunology

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“…On the contrary, in patients with inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease, there is a reduction of the expression of the trypsin inhibitor [44] [45] and thus, trypsin activity is increased in IBD patients [46]. Indeed, this phenomenon has also been observed in animal models of colitis [47]. Trypsin was also detected in the pancreatic parenchyma and pancreatic secretions of patients with pancreatitis, as well as in rodent models of experimental pancreatitis [48].…”

Section: Endogenous Proteases and Pain Related To Protease-activated mentioning

confidence: 95%

“…Nevertheless, a direct relationship between this increase and visceral pain was not investigated. Tryptase, another protease that can activate PAR 2 , constitutes the major protein released upon mucosal mast cell degranulation in humans, and is released in the setting of inflammation [47]. Trypsin and tryptase constitute good candidates to activate PAR 2 on DRG and could be responsible for the pain related to IBD.…”

Section: Endogenous Proteases and Pain Related To Protease-activated mentioning

confidence: 99%

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Cenac

2013

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Abstract:The protease-activated receptors (PARs) play a pivotal role in inflammatory and nociceptive processes. PARs have raised considerable interest because of their capacity to regulate numerous aspects of viscera physiology and pathophysiology. The present article summarizes research on PARs and proteases as signalling molecules in visceral pain. In particular, experiments in animal models suggest that PAR 2 is important for visceral hypersensitivity. Moreover, endogenous PAR 2 agonists seem to be released by colonic tissue of patients suffering from irritable bowel syndrome, suggesting a role for this receptor in visceral pain perception. Thus, PARs, together with proteases that activate them, represent exciting targets for therapeutic intervention on visceral pain.

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“…Increased numbers of hTryptase-β + MCs have been detected in intestinal specimens from patients with ulcerative colitis (UC) and Crohn disease (13). Colorectal biopsies from UC patients also constitutively released significantly more immunoreactive hTryptase-β into the conditioned medium than did colorectal biopsies from normal individuals (14). Nevertheless, it remains to be determined if MC-restricted tryptases have prominent proinflammatory activities in inflammatory bowel disease (IBD).…”

mentioning

confidence: 99%

Essential role for mast cell tryptase in acute experimental colitis

Hamilton

Sinnamon

Lyng³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

102

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Patients with inflammatory bowel disease (IBD) have increased numbers of human tryptase-β (hTryptase-β)-positive mast cells (MCs) in the gastrointestinal tract. The amino acid sequence of mouse mast cell protease (mMCP)-6 is most similar to that of hTryptase-β. We therefore hypothesized that this mMCP, or the related tryptase mMCP-7, might have a prominent proinflammatory role in experimental colitis. The dextran sodium sulfate (DSS) and trinitrobenzene sulfonic acid (TNBS) colitis models were used to evaluate the differences between C57BL/6 (B6) mouse lines that differ in their expression of mMCP-6 and mMCP-7 with regard to weight loss, colon histopathology, and endoscopy scores. Microarray analyses were performed, and confirmatory real-time PCR, ELISA, and/or immunohistochemical analyses were carried out on a number of differentially expressed cytokines, chemokines, and matrix metalloproteinases (MMPs). The mMCP-6-null mice that had been exposed to DSS had significantly less weight loss as well as significantly lower pathology and endoscopy scores than similarly treated mMCP-6-expressing mice. This difference in colitis severity was confirmed endoscopically in the TNBS-treated mice. Evaluation of the distal colon segments revealed that numerous proinflammatory cytokines, chemokines that preferentially attract neutrophils, and MMPs that participate in the remodeling of the ECM were all markedly increased in the colons of DSS-treated WT mice relative to untreated WT mice and DSS-treated mMCP-6-null mice. Collectively, our data show that mMCP-6 (but not mMCP-7) is an essential MC-restricted mediator in chemically induced colitis and that this tryptase acts upstream of many of the factors implicated in IBD.

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Release of Mast Cell Tryptase from Human Colorectal Mucosa in Inflammatory Bowel Disease

Cited by 127 publications

References 25 publications

Critical Role for Mast Cells in the Pathogenesis of 2,4-Dinitrobenzene-Induced Murine Colonic Hypersensitivity Reaction

Critical Role for Mast Cells in the Pathogenesis of 2,4-Dinitrobenzene-Induced Murine Colonic Hypersensitivity Reaction

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Essential role for mast cell tryptase in acute experimental colitis

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