Contribution of Plasma Proteinase Inhibitors to the Regulation of Activated Protein C in Plasma

Richard A Marlar; David C Kressin; Renee M Madden

doi:10.1055/s-0038-1651180

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1993; 69(01): 016-020
DOI: 10.1055/s-0038-1651180

Original Article

Coagulation

Schattauer GmbH Stuttgart

Contribution of Plasma Proteinase Inhibitors to the Regulation of Activated Protein C in Plasma

Richard A Marlar

The Departments of Biochemistry, Pathology and Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, and Laboratory Services, Denver Veterans Administration Medical Center, Denver, Colorado, USA

,

David C Kressin

The Departments of Biochemistry, Pathology and Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, and Laboratory Services, Denver Veterans Administration Medical Center, Denver, Colorado, USA

,

Renee M Madden

The Departments of Biochemistry, Pathology and Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, and Laboratory Services, Denver Veterans Administration Medical Center, Denver, Colorado, USA

› Institutsangaben

Abstract

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Summary

Activated protein C (APC), a serine protease, is regulated in plasma by protease inhibitors. This study was undertaken to determine the role of the major plasma inhibitors in regulating APC in plasma. Kinetic analysis and specific immunoassays for APC-inhibitor complexes were used to determine the inhibitors that form complexes with APC. Of the eight plasma inhibitors investigated, four interact with APC: protein C inhibitor (PCI), α₁-proteinase inhibitor (PI), α₂-antiplasmin (AP) and C1 esterase inhibitor (C1 Inh). The second order rate constants are: 1.3 × 10⁴ M⁻¹ s⁻¹ (PCI); 15 M⁻¹ s⁻¹ (PI); 410 M⁻¹ s⁻¹ (AP); and <6 M⁻¹ s⁻¹ (C1 Inh), with a relative effectiveness of each inhibitor to inactivate APC in plasma: 49:36:15:<1, respectively. PCI, PI and AP are the major inhibitors of APC in plasma. Low concentrations of APC will be inhibited by PCI with PI and AP playing a secondary role. However, as increasing APC is generated, PI and AP begin to play more important roles as the PCI is consumed.

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Referenzen

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