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(Circulation Research. 1996;78:596-605.)
© 1996 American Heart Association, Inc.

Articles

Regulation of ß₁-Integrin Function in Cultured Human Vascular Smooth Muscle Cells

Jiro Seki, Noriyuki Koyama, Nicholas L. Kovach, Ted Yednock, Alexander W. Clowes, John M. Harlan

From the Division of Hematology (J.S., N.L.K., J.M.H.), Harborview Medical Center, Seattle, Wash; the Department of Surgery (N.K., A.W.C.), University of Washington School of Medicine, Seattle; and Athena Neurosciences Inc (T.Y.), South San Francisco, Calif.

Correspondence to Jiro Seki, PhD, Department of Pharmacology, New Drug Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, 2-1-6 Kashima, Yodogawa-Ku, Osaka 532, Japan.

Abstract Avidity modulation and function of ß₁-integrin receptors in cultured human vascular smooth muscle cells (SMCs) were investigated using monoclonal antibody (mAb) 8A2, which binds to the ß₁ 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 ß₁ integrin was assessed with mAb 15/7, which binds to an activation-dependent epitope on the ß₁ 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 ß₁ 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 ß₁ integrin may play an important role in the function of SMCs.

Key Words: adhesion • migration • monoclonal antibody • extracellular matrix

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