Binding and activation of plasminogen at the surface of human keratinocytes.
Plasmin is thought to be involved in the pericellular proteolysis of the human epidermis under physiological and pathological conditions. Plasmin is provided by activation of the proenzyme plasminogen. We have explored in vitro whether plasminogen is bound and activated at the keratinocyte surface, a possible mechanism for providing plasmin in the pericellular space. Plasminogen and plasmin could be eluted from the surface of keratinocytes grown in serum-containing medium. When plasminogen was added to cultured keratinocytes it was activated by cell-associated urokinase-type plasminogen activator. The activation required plasminogen binding to the cell surface. Plasminogen binding by keratinocytes was saturable and proceeded in a time- and concentration-dependent manner. Surface-bound plasmin was rapidly displaced from the surface into the culture supernatant. When compared to plasmin in solution surface-bound plasmin was relatively protected from interaction with the specific inhibitor alpha 2-antiplasmin. Addition of exogenous plasmin or plasmin generation by the keratinocyte-associated plasminogen activators was ensued by the detachment of adherent keratinocytes in culture. Along the same line, plasmin counteracted keratinocyte adhesion to fibrin-coated but not to collagen-coated culture plates. The findings indicate that plasmin may be generated in the pericellular space of keratinocytes and may interfere with the adhesion to particular extracellular substrates.
Reinartz
J
J
Laboratory for Immunopathology, University of Heidelberg, Germany.
Batrla
R
R
Boukamp
P
P
Fusenig
N
N
Kramer
M D
MD
D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D013499:Surface Properties; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator