title: Regulation of beta1-integrin function in cultured human vascular smooth muscle cells.
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.
authors.affiliation: Division of Hematology, Harborview Medical Center, Seattle, Wash, USA.
authors.forename: J
authors.initials: J
authors.lastname: Seki
authors.forename: N
authors.initials: N
authors.lastname: Koyama
authors.forename: N L
authors.initials: NL
authors.lastname: Kovach
authors.forename: T
authors.initials: T
authors.lastname: Yednock
authors.forename: A W
authors.initials: AW
authors.lastname: Clowes
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
mesh_terms: D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D000939:Epitopes; D006801:Humans; D007231:Infant, Newborn; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D019012:Integrin beta1; D010982:Platelet-Derived Growth Factor