INTEGRIN MEDIATION OF ALVEOLAR EPITHELIAL-CELL MIGRATION ON FIBRONECTIN AND TYPE-I COLLAGEN

Acute lung injury leads to type I alveolar epithelial cell (AEC) death , denudation of the alveolar basement membrane, and formation of an al veolar provisional matrix from fibronectin, fibrinogen, and type I col lagen. The provisional matrix provides a scaffold for alveolar repair. To restore normal lung architecture, surviving type II AECs must reep ithelialize denuded alveoli. We examined whether AECs migrate on provi sional matrix proteins and whether integrins mediate this migration us ing a Boyden chemotaxis chamber. Cultured AECs migrated on fibronectin -coated filters by haptotaxis (defined as movement on a solid-phase su bstrate) more than on type I collagen-coated filters, and they did not migrate on fibrinogen-coated filters. Soluble fibronectin augmented m igration on type I collagen-coated filters, but not on fibronectin-coa ted filters. Anti-alpha(v) beta(3)-integrin monoclonal antibody (MAb) inhibited migration on substrate-bound fibronectin by 62-77%, whereas anti-beta(1)-integrin MAb inhibited migration by 48%. Anti-alpha(2)-in tegrin MAb almost completely inhibited migration on substrate-bound ty pe I collagen, but not on fibronectin. The novel findings in this stud y are as follows: 1) AECs migrate by haptotaxis more effectively on su bstrate-bound fibronectin than on type I collagen; 2) alpha(v) beta(3) - and beta(1)-integrins partially mediate AEC haptotaxis on fibronecti n; and 3) the alpha(2) beta(1)-integrin mediates AEC migration on type I collagen. These results support the importance of type II cell migr ation on provisional matrix proteins during repair of lung injury.