Published online before print August 16, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.061245

Accepted for publication June 29, 2007.

Article

Aberrant Mucosal Mast Cell Protease Expression in the Enteric Epithelium of Nematode-Infected Mice Lacking the Integrin _v6, a Transforming Growth Factor-₁ Activator

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

^@ To whom correspondence should be addressed. E-mail: pam.knight{at}ed.ac.uk.

	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)-1-dependent in vitro. TGF-1, which is secreted within tissues as a biologically inactive complex with latency-associated peptide, requires extracellular modification to become functionally active. The integrin-₆ mediates local activation of TGF-₁ in association with epithelia. Using T. spiralis-infected ₆^-/- 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 ₆^-/- mice compared with infected ₆^+/+ controls. Despite these changes, ₆^-/- mice still appeared to expel the worms normally. We postulate that compromised TGF-₁ 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 ₆^-/- mice.