The half-life of activated protein C (APC) was 31 min in citrated blood and 18 min in whole blood. Immunoblotting analysis of citrated blood identified APC-protein C inhibitor (APC-PCI) and APC-α1-antitrypsin complexes. Whole blood contained two additional APC-inhibitor complexes, one stimulated by Ca2+ and another by Mg2+. The former was identified as APC-α2-macroglobulin (APC-α2M) while the latter was not identified. APC-α2-antiplasmin complexes (APC-α2AP) were identified, comigrating with APC-PCI complexes. Purified α2M and α2AP inhibited APC in the presence of Ca2+ (k2 = 99 and 100 M-1 s-1, respectively. Inhibition of APC and Factor Xa by α2M and inhibition of APC by α2AP was stimulated by Ca2+, Mn2+, and Mg2+. Inhibition of thrombin by α2M and of plasmin by α2AP was not altered by EDTA or Ca2+, suggesting divalent metal ions affect APC and Factor Xa rather than the inhibitors. k2 values for the APC inhibitors and their plasma concentrations suggest that PCI and α1-antitrypsin are the more important APC inhibitors and that α2M and α2AP are metal ion-dependent auxiliary inhibitors. Inhibitors can account for the in vivo half-life of APC.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|State||Published - Nov 7 1991|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology