Activation of the cyclic AMP pathway in cells adhering to biomaterials: regulation by vitronectin- and fibronectin-integrin binding

Our previous studies have shown that cells adhering to biomaterials in seru m-free conditions increase their content of cyclic AMP (cAMP) and become ag gregated. In cells on an acrylonitrile membrane (AN69), these biochemical a nd morphological changes are prevented by adding 10% foetal calf serum (FCS ) to the medium; cells on the cellulose membrane Cuprophan (CU) remain unaf fected. The present study examines the roles of vitronectin (VN)- and/or fi bronectin (FN)-integrin binding in this inhibition. Competitively blocking VN- and FN-receptors with echistatin increased intracellular cAMP significa ntly and caused cells on AN69 to aggregate, but did not modify cAMP-depende nt cell aggregation on CU. VN or FN adsorbed onto CU also inhibited cAMP pr oduction by attached cells and prevented their aggregation, whereas adsorbe d BSA had no effect. Therefore, the binding of VN or FN to cell-surface int egrins seems to limit the activation of the cAMP pathway initiated by the s ubstratum itself. (C) 2000 Elsevier Science Ltd. All rights reserved.