Role of Specific Membrane Receptors in Urokinase-Dependent Migration of Human Keratinocytes

• Published in: Journal of investigative dermatology Vol. 94; no. 3; pp. 310 - 316
• Main Authors: Del Rosso, Mario, Fibbi, Gabriella, Dini, Germana, Grappone, Cecilia, Pucci, Marco, Caldini, Riccardo, Magnelli, Lucia, Fimiani, Michele, Lotti, Torello, Panconesi, Emiliano
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-1990
• Subjects: Antibodies, Monoclonal - immunology; Cell Movement - drug effects; Epidermal Cells; Epidermis - metabolism; Humans; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - physiology; Receptors, Cell Surface - physiology; Receptors, Urokinase Plasminogen Activator; Urokinase-Type Plasminogen Activator - immunology; Urokinase-Type Plasminogen Activator - pharmacology
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12874442

On the basis of both 125I-labeled plasminogen activator binding analysis and transmission electron microscopy studies of the interaction of a plasminogen activator/gold complex with cell membranes, we have found that human keratinocytes have specific receptors for human urokinase-type plasminogen activator distributed on the cell surface as singlets, or as small or large clusters. The use in binding experiments of the purified A chain of urokinase-plasminogen activator and of anti-A chain monoclonal antibodies has indicated that cell receptors are specific for a sequence present on the A chain, as previously reported for other cells. The interaction of both the native molecule and the purified A chain with such receptors stimulates mobilization of keratinocytes in an in vitro cell model system (Boyden chamber), when present in the lower compartment of the migration apparatus in nanomolar concentrations. Preincubation of chemoattractants with a monoclonal antibody which prevents receptor/ligand interaction also prevents plasminogen activator-induced cell migration. These data suggest that, under the conditions used in this in vitro model system, the plasminogen activator-dependent mobilization of keratinocytes depends on the interaction of the ligand with free receptors on the cell surface, and is independent of plasmin generation.