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.
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.
Pratt
C W
CW
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina.
Church
F C
FC
Pizzo
S V
SV
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood*; D006207:Half-Life; D015844:Heparin Cofactor II; D006801:Humans; D019272:Leukocyte Elastase; D046911:Macromolecular Substances; D008657:Metabolic Clearance Rate; D051379:Mice; D010196:Pancreatic Elastase / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000378:metabolism*; D014018:Tissue Distribution; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D006023:Glycoproteins; D046911:Macromolecular Substances; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D015844:Heparin Cofactor II; D000990:Antithrombin III; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D013917:Thrombin