PLASMA CARBOXYPEPTIDASES AS REGULATORS OF THE PLASMINOGEN SYSTEM

Carboxy-terminal lysine residues on the surface of cells and fibrin bi nd plasminogen and control its activation. Since plasma contains basic carboxypeptidases, which remove carboxy-terminal lysines from protein substrates, we investigated if these enzymes are involved in the regu lation of plasminogen binding sites, Plasma reduced plasminogen bindin g to cells, and this effect could be ascribed to the activity of the p lasma carboxypeptidases. Purified carboxypeptidase N, which is constit utively active, and plasma carboxypeptidase B, which circulates as a z ymogen, were both capable of significantly reducing plasminogen bindin g to cells. Dose titration experiments verified that plasma concentrat ions of either carboxypeptidase were sufficient to maximally affect pl asminogen binding to cells, Furthermore, plasma carboxypeptidase B, bu t not carboxypeptidase N, reduced the rate of whole blood clot lysis i nduced by tissue-type plasminogen activator. These findings establish that plasma carboxypeptidases can modulate plasminogen binding to cell s and control the rate of fibrinolysis. These functions delineate a no vel role for the plasma carboxypeptidases in the regulation of the pla sminogen system.