Published online before print August 16, 2007

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(American Journal of Pathology. 2007;171:1237-1248.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061245

Aberrant Mucosal Mast Cell Protease Expression in the Enteric Epithelium of Nematode-Infected Mice Lacking the Integrin _vß₆, a Transforming Growth Factor-ß₁ Activator

From the Department of Veterinary Clinical Studies, Easter Bush Veterinary Centre, The University of Edinburgh, Midlothian, United Kingdom

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)-ß1-dependent in vitro. TGF-ß1, which is secreted within tissues as a biologically inactive complex with latency-associated peptide, requires extracellular modification to become functionally active. The integrin-ß₆ mediates local activation of TGF-ß₁ in association with epithelia. Using T. spiralis-infected ß₆^–/– 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 ß₆^–/– mice compared with infected ß₆^+/+ controls. Despite these changes, ß₆^–/– mice still appeared to expel the worms normally. We postulate that compromised TGF-ß₁ 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 ß₆^–/– mice.