Regulation of beta1-integrin function in cultured human vascular smooth muscle cells
Seki, J.; Koyama, N.; Kovach, N.L.; Yednock, T.; Clowes, A.W.; Harlan, J.M.
Circulation Research 78(4): 596-605
1996
ISSN/ISBN: 0009-7330 PMID: 8635217 Document Number: 463227
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 extracellular 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 by a postreceptor mechanism. In addition, mAb 8A2 inhibited PDGF-BB-induced SMC migration through Matrigel-coated filters. These results suggest that avidity modulation of beta-1 integrin may play an important role in the function of SMCs.