Regulation of factor IXa in vitro in human and mouse plasma and in vivo in the mouse. Role of the endothelium and the plasma proteinase inhibitors
The regulation of human Factor IXa was studied in vitro in human and mouse plasma and in vivo in the mouse. In human plasma, approximately 60% of the /sup 125/I-Factor IXa was bound to antithrombin III (ATIII) by 2 h, with no binding to alpha 2-macroglobulin or alpha 1-proteinase inhibitor, as assessed by gel electrophoresis and IgG- antiproteinase inhibitor-Sepharose beads. In the presence of heparin, virtually 100% of the /sup 125/I-Factor IXa was bound to ATIII by 1 min. The distribution of /sup 125/I-Factor IXa in mouse plasma was similar. The clearance of /sup 125/I-Factor IXa was rapid (50% clearance in 2 min) and biphasic and was inhibited by large molar excesses of ATIII-thrombin and alpha 1-proteinase inhibitor-trypsin, but not alpha 2-macro-globulin-trypsin; it was also inhibited by large molar excesses of diisopropylphosphoryl - (DIP-) Factor Xa, DIP-thrombin, and Factor IX, but not by prothrombin or Factor X. The clearance of Factor IX was also rapid (50% clearance in 2.5 min) and was inhibited by a large molar excess of Factor IX, but not by large molar excesses of Factor X, prothrombin, DIP-Factor Xa, or DIP-thrombin. Electrophoresis and IgG- antiproteinase inhibitor-Sepharose bead studies confirmed that by 2 min after injection into the murine circulation, 60% of the /sup 125/I-Factor IXa was bound to ATIII. Organ distribution studies with /sup 125/I-Factor IXa demonstrated that most of the radioactivity was in the liver. These studies suggest that Factor IXa binds to at least two classes of binding sites on endothelial cells. One site apparently recognizes both Factors IX and IXa, but not Factor X, Factor Xa, prothrombin, or thrombin. The other site recognizes thrombin, Factor Xa, and Factor IXa, but not the zymogen forms of these clotting factors. After this binding, Factor IXa is bound to ATIII and the complex is cleared from the circulation by hepatocytes.
- Research Organization:
- Department of Pathology, Duke University Medical Center, Durham, North Carolina
- OSTI ID:
- 6885307
- Journal Information:
- J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 73:6; ISSN JCINA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Cleavage and activation of human factor IX by serine proteases
Binding of human factors X and Xa to HepG2 and J82 human tumor cell lines. Evidence that factor Xa binds to tumor cells independent of factor Va
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD COAGULATION FACTORS
BLOOD PLASMA
BODY FLUIDS
CHEMICAL BONDS
COAGULANTS
CONTROL
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
IN VITRO
IN VIVO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MATERIALS
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
RADIOISOTOPES
RODENTS
SERINE PROTEINASES
THROMBIN
TRACER TECHNIQUES
VERTEBRATES