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1 Regulates Adhesion of Mucosal Mast Cell Homologues to Laminin-1 Through Expression of Integrin
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Departments of
* Veterinary Pathology and
Veterinary Clinical Studies, University of Edinburgh, Roslin, Midlothian, United Kingdom; and
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-
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-
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-
1 to 58.7 ± 4.0% (p < 0.05) when
cultured mast cells had differentiated into MMC homologues in the
presence of TGF-
1. Increased adhesion of MMC homologues
to laminin-1 was also stimulated by Fc
RI cross-linking and the
calcium ionophore A23187. Expression of the laminin-binding integrin
7 by MMC homologues grown in the presence of TGF-
1
was demonstrated by RT-PCR and flow cytometry, and preincubation of MMC
homologues with the
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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