FUNCTIONAL SPECIALIZATION OF FIBRONECTIN-BINDING BETA(1)-INTEGRINS INT-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 det ermined using a modified Boyden chamber system. Adhesion studies of th e T cell lines indicated involvement of both alpha(4) beta(1) and alph a(5) beta(1) integrins in the binding to fibronectin. In contrast, mig ration assays demonstrated that haptotactic and chemotactic migration to fibronectin in most cases was mediated by only one of the beta(1) i ntegrins. FACS analysis demonstrated comparable amounts of alpha(4) be ta(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 fibron ectin fragment containing the RGD sequence, confirmed the selectivity of the different beta(1) integrins in directing migration. Thus, T cel ls using alpha(5) beta(1) for haptotaxis against fibronectin were migr ating 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 h aptotactic 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 t oxin and 8-Br-cAMP but not pertussis toxin inhibited migration of T ce ll lines to fibronectin. Adhesion of these cells to fibronectin was no t influenced by any of the toxins. Thus, both in their integrin utiliz ation and in their signaling pathways, adhesion and migration show sub stantial differences in T cells.