Turnover of *I-protein C inhibitor and *I-α1-antitrypsin and their complexes with activated protein C

Abstract

The rates of clearance and catabolism of human protein C inhibitor (PCI) and human α1-antitrypsin (α1-AT) and their complexes with human activated protein C (APC) were studied in the rabbit. The radioiodinated-free inhibitors had biologic half-lives of 23.4 and 62.1 hours, respectively, while the corresponding *I-labeled activated-protein C complexes were cleared with half-lives of 19.6 ± 3.1 and 72.2 ± 6.1 minutes. Complex clearances were linked to their catabolism as shown by a correlation between clearance and the appearance of free radioiodine in the plasma. Thus, the difference in the rates of catabolism would result in a fivefold greater amount of α1-AT-APC complex than PCI-APC complex 1 hour after the formation of equal amounts of these in vivo. These results lead to the conclusion that the relative contribution of PCI and α1-AT to the physiologic inhibition of APC cannot be determined only from the rates of the formation of these complexes in vitro, or from measurement of their levels in plasma. The APC-PCI complex is unstable as compared with the APC-α1-AT complex, compounding the problem of estimating rates of complex formation from their levels in plasma. © 1990 by The American Society of Hematology.