Imatinib mesylate alleviates diarrhea in a mouse model of intestinal allergy.

BACKGROUND: When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen-induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate. METHODS: Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT-PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease-1. Immunofluorescence staining was used to assess the intestinal CCL1 expression. KEY RESULTS: Ovalbumin-sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)-4 and -13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL-13, CCL1, CCL17 and CCL22. Mast cell-deficient W/W(-V) mice, and surprisingly, also their mast cell-competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain-dependent difference was associated with the inability of +/+ and W/W(-V) mice to increase the number of intestinal mast cells and expression of IL-4, IL-13, CCL1 and CCL17 after ovalbumin challenge. CONCLUSIONS & INFERENCES: Development of allergic diarrhea is associated with the ability of mice to develop intestinal mastocytosis. Imatinib inhibited the development of intestinal mastocytosis, reduced the incidence of diarrhea, and reduced the expression of IL-13, CCL1, and CCL17. Targeting intestinal mast cells could be a feasible approach to treat allergic diarrhea.

Mast cells associate with T-cells and neointimal microvessels in giant cell arteritis.

OBJECTIVE: Mast cells (MCs) are known to be involved in the neovascularization and regulation of T cell responses. However, the presence of MCs in giant cell arteritis (GCA) is unknown. This prompted us to study the presence and phenotype of MCs in GCA. METHODS: Human GCA specimens collected for diagnostic purposes were examined with immunohistochemistry. Double immunostainings of MC tryptase with cathepsin G, vascular endothelial cell growth factor (VEGF), CD3, and CD31/D34 were performed. RESULTS: Double immunostainings showed that activated tryptase-, cathepsin G- and VEGF-expressing MCs associate with CD3+ T cells and CD31/CD34+ neointimal neovessels in the GCA lesions. CONCLUSIONS: The results suggest that MCs may contribute to the pathogenesis of GCA putatively by regulating the functions of other inflammatory cells and resident vessel wall cells. Importantly, MCs promote neovascularization, which is considered as a prerequisite for the neointimal thickening in GCA.