title: Thrombin inhibition by HCII in the presence of elastase-cleaved HCII and thrombin-HCII complex.
abstract: The rate of thrombin inhibition by heparin cofactor II (HCII) is facilitated by heparin or dermatan sulfate in vitro. The distributions of these glycosaminoglycans (GAGs) in vivo are not the same; heparin-like substance is rich on the surface of endothelial cells and dermatan sulfate is relatively dominant in the extravascular region. When inflammation takes place, at least two other possible existent forms of HCII, the complexed form with thrombin and the cleaved form by leukocyte elastase, are assumed to be present at relatively high concentrations in a local circumstance. We examined the interactions of HCII with the two forms of HCII on thrombin inhibition in the presence of the GAGs. By HCII in complex with thrombin or cleaved by leukocyte elastase, the affinity of HCII moiety for heparin increases and that for dermatan sulfate decreases. The two forms possibly occur at relatively high concentrations in a local pathological situation, although the heparin cofactor activity for thrombin inhibition by HCII decreases and dermatan sulfate determines the cofactor activity. These results indicate efficient thrombin inhibitory activity of HCII in the extravascular region.
authors.affiliation: The First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan. hisato-tky@umin.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Maekawa
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: D M
authors.initials: DM
authors.lastname: Tollefsen
mesh_terms: D015844:Heparin Cofactor II / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D010196:Pancreatic Elastase / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D015842:Serine Proteinase Inhibitors; D015844:Heparin Cofactor II; D010196:Pancreatic Elastase; D013917:Thrombin