DIVALENT CATION-DEPENDENT REGULATION OF RAT ALVEOLAR EPITHELIAL-CELL ADHESION AND SPREADING

Interactions between cells and extracellular matrix are in large part mediated by integrins in divalent cation-dependent processes. Integrin s are important for cell differentiation, proliferation, and migration during development and repair of diverse tissue types. The roles play ed by integrin adhesion receptors in the lung are just beginning to be investigated. It is plausible that integrins play a central role in m ediating lung basement membrane influences on alveolar epithelial type II cell localization and differentiation. The current studies were ca rried out to determine the patterns of alveolar epithelial cell adhere nce and spreading on different substrata and their divalent cation and RGD requirements. We utilized a rat type II cell-derived cell line, L M5, and a human alveolar cell carcinoma cell line A549. Both cell type s showed similar responses to divalent cations. Adhesion and spreading on different extracellular matrix components had different divalent c ation requirements. Mn2+ enhanced adhesion and spreading on fibronecti n (FN), type IV collagen, and laminin, but not on type I collagen or p lastic. Mn2+-enhanced cell adhesion to FN was RGD-dependent and partia lly inhibited by an anti-alpha(5) integrin antibody. Small increases i n Ca2+ concentration (0.1-0.5 mM), but not Mg2+, suppressed Mn2+-media ted adhesion and spreading, Thus, variations in the relative divalent cation concentrations in the vicinity of the integrin-ligand complex m ay modulate the receptor-acceptor interactions. These results support the view that alterations in extracellular divalent cations are import ant regulators of alveolar epithelial cell interactions with lung base ment membrane. (C) 1994 Academic Press, Inc.