Regulation of beta(1)-integrin function in cultured human vascular smooth muscle cells

Avidity modulation and function of beta(1)-integrin receptors in cultured human vascular smooth muscle cells (SMCs) were investigated using monoclonal antibody (mAb) 8A2, which binds to the beta(1) subunit of integrin heterodimers and induces a high avidity state. The adhesion of SMCs to extra cellular matrix proteins, but not to poly-L-lysine, was enhanced by pretreatment with mAb 8A2. A qualitative alteration of beta(1) integrin was assessed with mAb 15/7, which binds to an activation-dependent epitope on the beta(1) subunit. Binding of mAb 15/7 was enhanced by mAb 8A2 in a dose-dependent manner. Arg-Gly-Asp peptide and soluble fibronectin also enhanced expression of the 15/7 epitope, suggesting that the 15/7 epitope is closely related to the ligand-occupied state of beta(1) integrin. Platelet-derived growth factor (PDGF)-AA and -BB increased SMC adhesion to type I collagen but did not augment mAb 15/7 binding, suggesting that PDGFs increase binding avidity bf a postreceptor mechanism. In addition mAb 8A2 inhibited PDGF-BB-induced SMC migration through Matri-gel-coated filters. These results suggest that avidity modulation of beta(1) integrin may play an important role in the Function of SMCs.