THE RECEPTOR FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR OF A HUMAN KERATINOCYTE LINE (HACAT)

It is assumed that plasmin participates in pericellular proteolysis in the epidermis. Plasmin is generated by keratinocyte-associated plasmi nogen activators from the proenzyme plasminogen; plasminogen activatio n can proceed at the keratinocyte surface. The resultant plasmin inter feres with cell to matrix adhesion and does possibly contribute to ker atinocyte migration during reepithelialization. Here we describe the r eceptor for urokinase-type plasminogen activator (uPA-R) in the human keratinocyte cell line HaCaT, which serves to direct plasminogen activ ation to the cell surface; we relate the receptor to the uPA-R previou sly described in human myelo-/monocytes. Binding of uPA to the recepto r accelerated plasminogen activation by a factor of approximate to 10, compared to uPA in solution. Receptor-bound uPA was susceptible to in hibition by the plasminogen activator inhibitors 1 and 2. uPA and uPA- R antigen, as well as uPA activity, were localized to the leading fron t of expanding sheets of HaCaT cells. Exposure of HaCaT cells to plasm inogen was followed by detachment of the cells. Detachment was prevent ed by an anticatalytic anti-uPA antibody, by the plasmin-specific inhi bitor aprotinin, and by the lysine analogue tranexamic acid, the latte r of which prevents plasmin(ogen) binding to the cell surface. Our fin dings support the hypothesis that uPA-mediated plasminogen activation is characteristic of mobile rather than sessile keratinocytes. Moreove r, the uPA-R seems to focalize plasminogen activation to the surface o f cells at the site of keratinocyte migration. (C) 1994 Academic Press , Inc.