Avidity modulation and function of beta(1)-integrin receptors in cultu
red human vascular smooth muscle cells (SMCs) were investigated using
monoclonal antibody (mAb) 8A2, which binds to the beta(1) subunit of i
ntegrin 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 be
ta(1) integrin was assessed with mAb 15/7, which binds to an activatio
n-dependent epitope on the beta(1) subunit. Binding of mAb 15/7 was en
hanced by mAb 8A2 in a dose-dependent manner. Arg-Gly-Asp peptide and
soluble fibronectin also enhanced expression of the 15/7 epitope, sugg
esting that the 15/7 epitope is closely related to the ligand-occupied
state of beta(1) integrin. Platelet-derived growth factor (PDGF)-AA a
nd -BB increased SMC adhesion to type I collagen but did not augment m
Ab 15/7 binding, suggesting that PDGFs increase binding avidity bf a p
ostreceptor mechanism. In addition mAb 8A2 inhibited PDGF-BB-induced S
MC migration through Matri-gel-coated filters. These results suggest t
hat avidity modulation of beta(1) integrin may play an important role
in the Function of SMCs.