Functional specialization of fibronectin-binding beta 1-integrins in T lymphocyte migration.
We have investigated the role of alpha 4 beta 1 and alpha 5 beta 1 integrins in adhesion and migration of T lymphocytes to extracellular matrix proteins. Fibronectin, collagen type IV, and laminin promoted haptotactic and chemotactic migration of lymphoid T cell lines and 12-O-tetradecanoylphorbol 13-acetate-stimulated blood lymphocytes, as determined using a modified Boyden chamber system. Adhesion studies of the T cell lines indicated involvement of both alpha 4 beta 1 and alpha 5 beta 1 integrins in the binding to fibronectin. In contrast, migration assays demonstrated that haptotactic and chemotactic migration to fibronectin in most cases was mediated by only one of the beta 1 integrins. FACS analysis demonstrated comparable amounts of alpha 4 beta 1 and alpha 5 beta 1 on the various cell lines, indicating that utilization of the integrins for migration is not determined by their expression on the cells. Haptotactic migration toward a 120-kDa fibronectin fragment containing the RGD sequence, confirmed the selectivity of the different beta 1 integrins in directing migration. Thus, T cells using alpha 5 beta 1 for haptotaxis against fibronectin were migrating against the 120 kDa fragment whereas T cells using alpha 4 beta 1 were not. These results indicate that the response of T cells to haptotactic and chemotactic signals usually is mediated selectively via alpha 4 beta 1 or alpha 5 beta 1 although binding of fibronectin to the cells is not restricted to only one of the integrins. Cholera toxin and 8-Br-cAMP but not pertussis toxin inhibited migration of T cell lines to fibronectin. Adhesion of these cells to fibronectin was not influenced by any of the toxins. Thus, both in their integrin utilization and in their signaling pathways, adhesion and migration show substantial differences in T cells.
Department of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden.
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Hauzenberger
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Klominek
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KG
Sundqvist
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D000595:Amino Acid Sequence; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides; D037342:Pertussis Toxin; D017469:Receptors, Fibronectin / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; D016023:Integrins; D007797:Laminin; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D010566:Virulence Factors, Bordetella; D015124:8-Bromo Cyclic Adenosine Monophosphate; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen; D002772:Cholera Toxin; D037342:Pertussis Toxin