Regulation of beta1-integrin function in cultured human vascular smooth muscle cells

Circ Res. 1996 Apr;78(4):596-605. doi: 10.1161/01.res.78.4.596.

Abstract

Avidity modulation and function of beta1-integrin receptors in cultured human vascular smooth muscle cells (SMCs) were investigated using monoclonal antibody (mAb) 8A2, which binds to the beta1 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 beta1 integrin was assessed with mAb 15/7, which binds to an activation-dependent epitope on the beta1 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 beta1 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 beta1 integrin may play an important role in the function of SMCs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Epitopes
  • Humans
  • Infant, Newborn
  • Integrin beta1 / immunology
  • Integrin beta1 / physiology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Platelet-Derived Growth Factor / pharmacology

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • Integrin beta1
  • Platelet-Derived Growth Factor