In vivo regulation of plasminogen function by plasma carboxypeptidase B

Carmen M Swaisgood ¹, Detlef Schmitt , Dan Eaton

⁰Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

The Journal of Clinical Investigation +

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November 6, 2002

View abstract on PubMed

Summary

Plasma carboxypeptidase B (pCPB) suppresses plasminogen (Plg) functions. Mice lacking pCPB showed increased fibrinolysis and leukocyte migration, confirming pCPB

Area Of Science

Biochemistry
Physiology
Molecular Biology

Background

Plasminogen (Plg) functions in fibrinolysis and cell migration are crucial and depend on binding to carboxy-terminal lysyl residues.
Plasma carboxypeptidase B (pCPB) removes these lysyl residues, suggesting a potential suppressive role in Plg-dependent processes.

Purpose Of The Study

To investigate the in vivo role of plasma carboxypeptidase B (pCPB) as a suppressor of plasminogen (Plg) functions.
To evaluate the impact of pCPB deficiency on fibrinolysis and leukocyte migration in a mouse model.

Main Methods

Generation of pCPB-deficient mice (pCPB(-/-)) via homologous recombination.
Cross-mating of pCPB(-/-) mice with Plg-deficient mice (Plg(-/-)) to create Plg(+/-)/pCPB(+/-) and Plg(+/-)/pCPB(-/-) mouse models.
Assessment of fibrinolysis using a pulmonary clot lysis model and leukocyte migration in a thioglycollate-induced peritoneal inflammation model.

Main Results

Fibrinolysis was significantly enhanced in pCPB-deficient mice (both partial and total deficiency) compared to wild-type controls in a pulmonary clot lysis model.
Leukocyte migration at 72 hours was significantly increased in mice with partial or total absence of pCPB in a peritoneal inflammation model.
These findings were observed in a background of partial plasminogen deficiency (Plg(+/-)).

Conclusions

Plasma carboxypeptidase B (pCPB) plays a definitive role in modulating the essential functions of plasminogen (Plg) in vivo.
pCPB acts as a suppressor of Plg-dependent fibrinolysis and leukocyte migration.

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