Expression of integrin-alphaE by mucosal mast cells in the intestinal epithelium and its absence in nematode-infected mice lacking the transforming growth factor-beta1-activating integrin alphavbeta6.
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(E)beta(7) 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(E)beta(7) and the MMC chymase mouse mast cell protease-1, by mouse bone marrow-derived mast cells, is strictly regulated by transforming growth factor (TGF)-beta(1). However, TGF-beta(1) 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(E)beta(7) in Trichinella-infected BALB/c and S129 mice. In S129 mice that lack the gene for the integrin-beta(6) subunit and, as consequence, do not express the epithelial integrin-alpha(v)beta(6), 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(v)beta(6) is to activate latent TGF-beta(1,) these findings strongly support a role for TGF-beta(1) in both the recruitment and differentiation of murine MMCs during nematode infection.
Brown
Jeremy K
JK
Department of Veterinary Clinical Studies, Easter Bush Veterinary Centre, the University of Edinburgh, Midlothian, Scotland, United Kingdom. jeremy.brown2@ed.ac.uk
Knight
Pamela A
PA
Pemberton
Alan D
AD
Wright
Steven H
SH
Pate
Judith A
JA
Thornton
Elisabeth M
EM
Miller
Hugh R P
HR
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics; D015153:Blotting, Western; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D017353:Gene Deletion; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000378:metabolism*; D016023:Integrins / Q000172:deficiency* / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology / Q000469:parasitology; D007583:Jejunum / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009349:Nematode Infections / Q000150:complications* / Q000276:immunology / Q000469:parasitology; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D017160:Trichinella spiralis / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D039001:Integrin alpha Chains; D016023:Integrins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C091367:alpha E integrins; C073878:integrin alphavbeta6; D012313:RNA; D016650:Fluorescein-5-isothiocyanate