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The Journal of Immunology, 2002, 169: 5689-5695.
Copyright © 2002 by The American Association of Immunologists

TGF-{beta}1 Regulates Adhesion of Mucosal Mast Cell Homologues to Laminin-1 Through Expression of Integrin {alpha}71

Anne Rosbottom*, Cheryl L. Scudamore2,*, Helga von der Mark{ddagger}, Elizabeth M. Thornton{dagger}, Steven H. Wright{dagger} and Hugh R. P. Miller3,{dagger}

Departments of * Veterinary Pathology and {dagger} Veterinary Clinical Studies, University of Edinburgh, Roslin, Midlothian, United Kingdom; and {ddagger} Institute of Experimental Medicine, Friedrich Alexander University, Erlangen, Germany

Mucosal mast cells (MMC) or their precursors migrate through the intestinal lamina propria to reside intraepithelially, where expression of mouse mast cell protease-1 indicates the mature phenotype. Alterations in expression of integrins that govern cell adhesion to the extracellular matrix may regulate this process. As the key cytokine mediating differentiation of mouse mast cell protease-1-expressing MMC homologues in vitro, TGF-{beta}1 was considered a likely candidate for regulation of the integrins that facilitate intraepithelial migration of MMC. Therefore, we examined adhesion of bone marrow-derived mast cells cultured with and without TGF-{beta}1 to laminin-1, fibronectin, and vitronectin along with expression of integrins likely to regulate this adhesion. Adhesion of PMA-stimulated cultured mast cells to laminin-1 increased from 5.3 ± 3.6% (mean ± SEM) in the absence of TGF-{beta}1 to 58.7 ± 4.0% (p < 0.05) when cultured mast cells had differentiated into MMC homologues in the presence of TGF-{beta}1. Increased adhesion of MMC homologues to laminin-1 was also stimulated by Fc{epsilon}RI cross-linking and the calcium ionophore A23187. Expression of the laminin-binding integrin {alpha}7 by MMC homologues grown in the presence of TGF-{beta}1 was demonstrated by RT-PCR and flow cytometry, and preincubation of MMC homologues with the {alpha}7-neutralizing Ab 6A11 inhibited adhesion to laminin-1 by 98% (p < 0.05), demonstrating a novel role for this molecule in adhesion of a hemopoietic cell to laminin-1.




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