INTEGRIN ALPHA(6)BETA(4) MEDIATES DYNAMIC INTERACTIONS WITH LAMININ

We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha(6) beta(4)-positive cells in the presence of fluid shear stress (tau less than or equal to 2 dyn/cm(2)), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm(2) less than or equal to tau less than or equal to 100 dyn/cm(2)) dyn/cm(2)) initiated rolling of attached cells in the direction of how, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which interacts with alpha(6) integrins, supported dynamic attachment and rolling but extracellular matrix glycoprotein fibronectin did not. In cell lines that express alpha(6) beta(4) but not alpha(6) beta(1) an anti-alpha(6) monoclonal antibody inhibited attachment to laminin in the presence of flow and following 5 minutes of static incubation. Infusion of this antibody onto cells adherent to laminin-coated slides led to rapid detachment of cells from the substratum. An anti-beta(1) monoclonal antibody diminished adhesion strength following static incubation but did not inhibit rapid attachment and flow-initiated rolling. These results indicate that in some alpha(6) beta(4)-expressing epithelial and carcinoma cell lines, integrin alpha(6) beta(4) mediates rapidly formed dynamic interactions with laminin.