TGF-beta 1 regulates adhesion of mucosal mast cell homologues to laminin-1 through expression of integrin alpha 7.
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-beta1 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-beta1 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-beta1 to 58.7 +/- 4.0% (p < 0.05) when cultured mast cells had differentiated into MMC homologues in the presence of TGF-beta1. Increased adhesion of MMC homologues to laminin-1 was also stimulated by FcepsilonRI cross-linking and the calcium ionophore A23187. Expression of the laminin-binding integrin alpha(7) by MMC homologues grown in the presence of TGF-beta1 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.
Rosbottom
Anne
A
Department of Veterinary Pathology, University of Edinburgh, Roslin, Midlothian, UK EH25 9RG.
Scudamore
Cheryl L
CL
von der Mark
Helga
H
Thornton
Elizabeth M
EM
Wright
Steven H
SH
Miller
Hugh R P
HR
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007073:Immunoglobulin E / Q000494:pharmacology; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D016023:Integrins / Q000096:biosynthesis / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects; D019096:Vitronectin / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; D017077:Culture Media, Conditioned; D005353:Fibronectins; D039001:Integrin alpha Chains; D016023:Integrins; D007797:Laminin; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019096:Vitronectin; C085725:integrin alpha7; C121346:laminin 1; D007073:Immunoglobulin E; D000001:Calcimycin