The role of integrins in saphenous vein vascular smooth muscle cell migration.
OBJECTIVE
Smooth muscle cell (SMC) migration is an essential feature of the intimal hyperplastic process that so frequently limits the patency of vascular reconstructions. The purpose of this investigation was to evaluate the effect of a series of integrins, or cell surface receptors that mediate cellular attachment, on platelet-derived growth factor (PDGF) and extracellular matrix (ECM) protein-induced migration of human SMCs.


METHODS
Immunofluorescence staining was used to search for various integrins and subunits on the surface of SMCs derived from human saphenous vein. Chemotaxis and haptotaxis of SMCs to various matrix proteins and PDGF were assayed using a 48-well microchemotaxis chamber in the presence or absence of antibodies that blocked the function of these integrins.


RESULTS
Several subunits (beta 1, alpha 2, alpha 5) and one integrin (alpha v beta 3) were identified in saphenous vein SMCs. The beta 1 integrin antibody inhibited chemotaxis to collagen I and IV, laminin, and PDGF. The alpha 2 integrin antibody inhibited collagen I and IV, and laminin-induced chemotaxis. The alpha 5 integrin antibody had no effect on SMC migration. The alpha v beta 3 integrin antibody inhibited chemotaxis to PDGF but not to the ECM proteins.


CONCLUSIONS
Integrins are necessary for SMC migration induced by PDGF and ECM proteins. The integrin or subunits responsible for facilitating migration varies with the stimulant. Agonists designed to inhibit integrin function might be used to suppress SMC migration and suppress the formation of intimal hyperplasia.
Itoh
H
H
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Nelson
P R
PR
Mureebe
L
L
Horowitz
A
A
Kent
K C
KC
D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012501:Saphenous Vein / Q000166:cytology; D017539:Tunica Intima / Q000473:pathology
D016326:Extracellular Matrix Proteins; D016023:Integrins; D010982:Platelet-Derived Growth Factor