In vivo catabolism of heparin cofactor II and its complex with thrombin: evidence for a common receptor-mediated clearance pathway for three serine proteinase inhibitors.

Journal Article

The plasma clearance of 125I-labeled human heparin cofactor II and its complex with thrombin was studied in mice to determine whether a specific mechanism exists for the catabolism of the inhibitor-proteinase complex. Initial studies demonstrated that murine plasma contains a heparin cofactor II-like inhibitor as shown by the presence of a dermatan sulfate-sensitive thrombin inhibitor. Human heparin cofactor II cleared from the circulation of mice with an apparent half-life of 80 min while heparin cofactor II-thrombin complexes cleared with an apparent half-life of only 10 min. The specificity of the clearance mechanism was investigated by clearance competition studies involving coinjection of excess unlabeled heparin cofactor II-alpha-thrombin, antithrombin III-alpha-thrombin, or alpha 1-proteinase inhibitor-elastase, and by tissue distribution studies. The results demonstrated that the clearance of 125I-labeled heparin cofactor II-alpha-thrombin is a receptor-mediated process, and that the same hepatocyte receptor system recognizes complexes containing heparin cofactor II, antithrombin III, and alpha 1-proteinase inhibitor.

Full Text

Duke Authors

Cited Authors

  • Pratt, CW; Church, FC; Pizzo, SV

Published Date

  • April 1, 1988

Published In

Volume / Issue

  • 262 / 1

Start / End Page

  • 111 - 117

PubMed ID

  • 3258496

International Standard Serial Number (ISSN)

  • 0003-9861

Language

  • eng

Conference Location

  • United States