BETA-1 AND BETA-3 INTEGRINS HAVE DIFFERENT ROLES IN THE ADHESION AND MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS ON EXTRACELLULAR-MATRIX

Extracellular matrix receptors on ductus arteriosus smooth muscle cells (SMC) must enable the cells to migrate through both interstitial and basement membrane matrices to form intimal mounds during postnatal ductus closure. We examined the role of β1 and β3 integrin receptors on SMC adhesion and migration. Using a new assay to measure cell migration, we found that lamb ductus arteriosus SMC attach to and migrate over surfaces coated with fibronectin (FN), laminin (LN), vitronectin (VN), and collagens I (I) and IV (IV). Blocking antibodies, specific to different integrin complexes, showed that SMC adhesion to FN, LN, I, and IV depended exclusively on functioning β1 integrins with little, if any, contribution by the αvβ3 integrin; on the other hand, cell migration over these substrates depended to a large extent on the αvβ3 receptor. Immunofluorescent staining demonstrated that during the early phase of SMC migration, the β1 integrins organized rapidly into focal plaques that, with time, gradually covered the cell's basal surface; on the other hand, the β3 receptor remained concentrated at all times at the cell's margins. Ligand affinity chromatography and immunoprecipitation techniques identified a unique series of β1 integrins binding to each matrix component: FN (α5β1, α3β1, αvβ1), LN (α1β1, α7β1), VN (αvβ1), I (α1β1, α2β1), and IV (α1β1). In contrast, the β3 integrin, αvβ3, bound to all the substrates tested: FN, LN, VN, I, and IV. The results indicate that β1 and β3 integrins may play different roles in attachment and migration as SMC move through the vascular extracellular matrix to produce obliteration of the ductus arteriosus lumen. © 1992.