PLASMIN ABROGATES ALPHA(V)BETA(5)-MEDIATED ADHESION OF A HUMAN KERATINOCYTE CELL-LINE (HACAT) TO VITRONECTIN

At cellular surfaces, urokinase-type plasminogen activator (uPA) is bo und to a specific receptor (uPA-R). When bound to this receptor, uPA a ctivates plasminogen, which is derived from plasma or the interstitial fluids. Thus, plasmin is provided for proteolysis of pericellular pro teinaceous substrates. Here we demonstrate by immunocytology and laser scan microscopy that in the human keratinocyte cell line HaCaT uPA-R and uPA are localized together with the integrin alpha(v) beta(5) ill focal contacts. Via the integrin alpha(v) beta(5), HaCaT cells adhere to vitronectin in a ROD-dependent manner. Plasmin interfered with the alpha(v) beta(5)-mediated keratinocyte adhesion to vitronectin, most l ikely via cleavage of vitronectin and destruction of its cell binding function. Our findings demonstrate that plasmin, when generated by the uPA-dependent cell surface-associated pathway of plasminogen activati on, can abrogate the cell-binding function of vitronectin and can thus disturb the adhesive interaction with this matrix molecule, In focal contacts molecules are assembled that are crucial for adhesion to vitr onectin (i.e., the integrin alpha(v) beta(5)), as well as for the gene ration of plasmin (i.e., uPA-R and uPA), which can negatively influenc e the binding interaction. We suggest that the plasmin-mediated abroga tion of the interaction between the integrin alpha(v) beta(5) and vitr onectin is a pathway of negative regulation; the codistribution of uPA -R/uPA and alpha(v) beta(5) in focal contacts may restrict this proces s to areas of cell/matrix contact. (C) Academic Press, Inc.