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(American Journal of Pathology. 2004;165:95-106.)
© 2004 American Society for Investigative Pathology

Expression of Integrin-{alpha}E by Mucosal Mast Cells in the Intestinal Epithelium and Its Absence in Nematode-Infected Mice Lacking the Transforming Growth Factor-ß1-Activating Integrin {alpha}vß6

Jeremy K. Brown, Pamela A. Knight, Alan D. Pemberton, Steven H. Wright, Judith A. Pate, Elisabeth M. Thornton and Hugh R. P. Miller

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

Peak intestinal mucosal mast cell (MMC) recruitment coincides with expulsion of Trichinella spiralis, at a time when the majority of the MMCs are located within the epithelium in BALB/c mice. Although expression of integrin-{alpha}Eß7 by MMCs has not been formally demonstrated, it has been proposed as a potential mechanism to account for the predominantly intraepithelial location of MMCs during nematode infection. Co-expression of integrin-{alpha}Eß7 and the MMC chymase mouse mast cell protease-1, by mouse bone marrow-derived mast cells, is strictly regulated by transforming growth factor (TGF)-ß1. However, TGF-ß1 is secreted as part of a latent complex in vivo and subsequent extracellular modification is required to render it biologically active. We now show, for the first time, that intraepithelial MMCs express integrin-{alpha}Eß7 in Trichinella-infected BALB/c and S129 mice. In S129 mice that lack the gene for the integrin-ß6 subunit and, as consequence, do not express the epithelial integrin-{alpha}vß6, integrin-{alpha}E expression is virtually abolished and recruitment of MMCs into the intestinal epithelium is dramatically reduced despite significant overall augmentation of the MMC population. Because a major function of integrin-{alpha}vß6 is to activate latent TGF-ß1, these findings strongly support a role for TGF-ß1 in both the recruitment and differentiation of murine MMCs during nematode infection.





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