Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator.
On the basis of a fibrinolytic assay with 125I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, we have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration (5 ng/ml) which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, we hypothesize that this mechanism may be important in vivo during the process of wound repair.
Fibbi
G
G
Institute of General Pathology of Florence University, Italy.
Magnelli
L
L
Pucci
M
M
Del Rosso
M
M
D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D010960:Plasminogen Activators / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D004792:Enzyme Precursors; D046911:Macromolecular Substances; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator