Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease

Bischoff, Stephan C.; Wedemeyer, Jochen; Herrmann, Alena; Meier, Pascal; Trautwein, C; Cetin, Yalcin; Maschek, H.; Stolte, Manfred; Gebel, M.; Manns, Michael P.

doi:10.1046/j.1365-2559.1996.262309.x

Cited by 242 publications

(166 citation statements)

References 34 publications

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“…Most experts agree that IBD is a consequence of abnormal immune responses to intestinal lumen pathogens and exogenous antigens (25). Because increased numbers of activated and degranulating MCs have been found in IBD patients (26,27), we hypothesized that MCs and one or more of their granule protease mediators Fig. 6.…”

Section: Discussionmentioning

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.

107

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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Section: Discussionmentioning

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.

107

102

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“…Mast cells in the lamina propria and submucosa have been implicated as contributors to local inflammation during IBD because of their ability to synthesize mediators such as histamine, prostaglandins, leukotrienes, cytokines, chemokines, and proteases. 15,35,36 The W sh mice were found to be more resistant to DSS-induced weight loss and mucosal damage in the cecum than C57BL/6 mice, a process that was confirmed to be mast cell-dependent by reconstitution studies. Mast cells have been shown by a number of groups to modify the epithelial barrier function within the intestine and, when activated, to increase intestinal permeability and fluid loss.…”

Section: Discussionmentioning

confidence: 80%

“…15,35,36 To date, no reported studies have examined the contribution of the mast cell during DSS colitis using mast cell-deficient Kit W-sh/W-sh (W sh ) mice. Mast cell-deficient mice, wild-type C57BL/6, and W sh mice reconstituted intravenously with 7.5 ϫ 10 6 C57BL/6 BMMCs were all treated with 3% DSS for 5 days, followed by 2 or 5 days of regular drinking water.…”

Section: Mast Cell-deficient W Sh Mice Are Less Susceptible Than Wildmentioning

confidence: 99%

“…12,13 An increase in eosinophil numbers has also been reported in subsets of IBD patients. 14,15 Eosinophil numbers are known to be significantly increased in the mucosa and submucosa of the colon in C57BL/6 mice after dextran sodium sulfate (DSS) treatment, a well characterized and widely used model of inducible colitis. 16,17 Moreover, this eosinophil recruitment was highly dependent on the activity of CCL11.…”

mentioning

confidence: 99%

“…29 -34 Mast cells have been suggested to play a proinflammatory role in models of colitis, and there is some evidence of mast cell activation in human IBD. 15,35,36 Mast cells are considered an important source of cytokines, chemokines, and other signaling factors that initiate the recruitment of eosinophils into sites of allergic inflammation. [37][38][39] Specifically, in the gastrointestinal tract mucosal mast cells can produce significant amounts of IL-5, CCL11, and LTC 4 after IgE-mediated stimulation, making them key cells to study in disease processes associated with eosinophilia.…”

mentioning

confidence: 99%

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Tissue Eosinophilia in a Mouse Model of Colitis Is Highly Dependent on TLR2 and Independent of Mast Cells

Albert

Duplisea

Dawicki

et al. 2011

The American Journal of Pathology

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The mechanisms initiating eosinophil influx into sites of inflammation have been well studied in allergic disease but are poorly understood in other settings. This study examined the roles of TLR2 and mast cells in eosinophil accumulation during a nonallergic model of eosinophilia-associated colitis. TLR2-deficient mice (TLR2 ؊/؊ ) developed a more severe colitis than wild-type mice in the dextran sodium sulfate (DSS) model. However, they had significantly fewer eosinophils in the submucosa of the cecum (P < 0.01) and mid-colon (P < 0.01) than did wild-type mice after DSS treatment. Decreased eosinophilia in TLR2 ؊/؊ mice was associated with lower levels of cecal CCL11 (P < 0.01). Peritoneal eosinophils did not express TLR2 protein, but TLR2 ligand injection into the peritoneal cavity induced local eosinophil recruitment, indicating that TLR2 activation of other cell types can mediate eosinophil recruitment. After DSS treatment, mast celldeficient (Kit W-sh/W-sh ) mice had similar levels of intestinal tissue eosinophilia were observed as those in wild-type mice. However, mast cell-deficient mice were partially protected from DSS-induced weight loss, an effect that was reversed by mast cell reconstitution. Overall, this study indicates a critical role for indirect TLR2-dependent pathways, but not mast cells, in the generation of eosinophilia in the large intestine during experimental colitis and has important implications for the regulation of eosinophils at mucosal inflammatory sites.

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