Activation of Plasma Procarboxypeptidase U in Different Mammalian Species Points to a Conserved Pathway of Inhibition of Fibrinolysis

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Abstract
Carboxypeptidase U (CPU, EC 3.4.17.20) is a recently described basic carboxypeptidase which circulates in plasma as the zymogen procarboxypeptidase U (proCPU). In the current study, we report on the presence of the proCPU/CPU system in different mammalian species – pig, guinea pig, dog, mouse, rabbit, rat and human. The proCPU concentration, determined as carboxypeptidase activity following thrombin-thrombomodulin activation, ranged from 255 U/l (mouse) to 5051 U/l (pig). When the CPU activity is generated during controlled in vitro coagulation by recalcifying citrated plasma, consistently lower activities were found compared to thrombin-thrombomodulin activation. These data indicate that in all species studied the mechanism for activation of proCPU is present. We demonstrate that in all species studied the addition of PTCI – a CPU inhibitor – results in a marked reduction of the lysis time. Albeit the presence of proCPU, the mechanism of activation during coagulation and the substantial reduction of the clot lysis time in the presence of PTCI point to a conserved inhibitory pathway of fibrinolysis.