Abstract
Infection of mice with the nematode Trichinella spiralis triggers recruitment and differentiation of intraepithelial intestinal mucosal mast cells expressing mouse mast cell protease 1 (Mcpt-1), which contributes to expulsion of the parasite. Expression of Mcpt-1 is transforming growth factor (TGF)-β1-dependent in vitro. TGF-β1, which is secreted within tissues as a biologically inactive complex with latency-associated peptide, requires extracellular modification to become functionally active. The integrin-ανβ6 mediates local activation of TGF-β1 in association with epithelia. Using T. spiralis-infected β6−/− mice, we show accumulation of mucosal mast cells in the lamina propria of the small intestine with minimal recruitment into the epithelial compartment. This was accompanied by a coordinate reduction in expression of both Mcpt-1 and -2 in the jejunum and increased tryptase expression, whereas Mcpt-9 became completely undetectable. In contrast, the cytokine stem cell factor, a regulator of mast cell differentiation and survival, was significantly up-regulated in T. spiralis-infected β6−/− mice compared with infected β6+/+ controls. Despite these changes, β6−/− mice still appeared to expel the worms normally. We postulate that compromised TGF-β1 activation within the gastrointestinal epithelial compartment is a major, but not the only, contributing factor to the observed changes in mucosal mast cell protease and epithelial cytokine expression in β6−/− mice.
Original language | English |
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Pages (from-to) | 1237-1248 |
Number of pages | 12 |
Journal | The American Journal of Pathology |
Volume | 171 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 2007 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Antigens, Neoplasm
- Bone Marrow
- Chymases
- Colon
- Cytokines
- Ear
- Integrins
- Intestinal Mucosa
- Jejunum
- Mast Cells
- Mice
- Mice, Mutant Strains
- Stomach
- Transforming Growth Factor beta1
- Trichinella spiralis
- Trichinellosis