Plasmin Abrogates αvβ5-Mediated Adhesion of a Human Keratinocyte Cell Line (HaCaT) to Vitronectin

• Published in: Experimental cell research 1995-10, Vol.220 (2), p.274-282
• Main Authors: Reinartz, Jeannette, Schafer, Birgit, Batrla, Richard, Klein, C.Eberhard, Kramer, Michael D.
• Format: Article
• Language: English
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.1995.1316

At cellular surfaces, urokinase-type plasminogen activator (uPA) is bound to a specific receptor (uPA-R). When bound to this receptor, uPA activates plasminogen, which is derived from plasma or the interstitial fluids. Thus, plasmin is provided for proteolysis of pericellular proteinaceous 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 αvβ5 in focal contacts. Via the integrin αvβ5, HaCaT cells adhere to vitronectin in a RGD-dependent manner. Plasmin interfered with the αvβ5-mediated keratinocyte adhesion to vitronectin, most likely 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 activation, 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 vitronectin (i.e., the integrin αvβ5), as well as for the generation of plasmin (i.e., uPA-R and uPA), which can negatively influence the binding interaction. We suggest that the plasminmediated abrogation of the interaction between the integrin αvβ5 and vitronectin is a pathway of negative regulation; the codistribution of uPA-R/uPA and αvβ5 in focal contacts may restrict this process to areas of cell/matrix contact.