Diagnostic assays using soluble endothelial cell protein C/activ

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

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435 78, 435975, 436506, 5303871, 53038822, 5303891, G01N 3353, G01N 33564, C07K 1628

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058043926

ABSTRACT:
Plasma EPCR has been isolated, characterized and shown to block cellular protein C activation and APC anticoagulant activity. Plasma EPCR appears to be about 43,000 daltons and circulates at approximately 100 ng/ml (98.4.+-.27.8 ng/ml, n=22). Plasma EPCR bound activated protein C with an affinity similar to that of recombinant soluble EPCR (Kd.sub.app approximately 30 nM), and inhibits both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage factor Xa clotting assay. Soluble plasma EPCR appears to attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of activated protein C. Soluble EPCR has also been detected in urine. Levels of soluble EPCR can rise in inflammatory disease associated with vascular injury and appear to be correlated with inflammation and disease states associated with abnormal coagulation. Since EPCR expression is restricted to larger vessels and is usually negative in cappillaries, these observations provide a mechanism for analyzing injury/stimulation of large vessel endothelial cells.

REFERENCES:
patent: 4782137 (1988-11-01), Hopp et al.
patent: 5009889 (1991-04-01), Taylor et al.
patent: 5298599 (1994-03-01), Rezaie et al.
patent: 5695993 (1997-12-01), Fukudome et al.
Boehme, et al., "Release of thrombomodulin from endothelial cells by concentrated action of TNF-.alpha. and neutrophils: in vivo and in vitro studies," Immunology 87:134-140 (1996).
Bourin and Lindahl, "Review Article: Glycosaminoglycans and the regulation of blood coagulation," Biochem. J. 289:313-330 (1993).
Conway and Rosenberg, "Tumor Necrosis Factor Suppresses Transcription of the Thrombomodulin Gene in Endothelial Cells," Mol. Cell. Biol. 8(12):5588-5592 (1988).
Dahlback, "Protein S and C4b-Binding Protein: Components Involved in the Regulation of the Protein C Anticoagulant System," Thromb. Haemostas. 66:49-61 (1991).
Dahlback, "Inhibition of Protein C.sub.a Cofactor Function of Human and Bovine Protein S by C4b-binding Protein," J. Biol. Chem. 261(26):12022-12027 (1986).
Dittman, W. A. "Thrombomodulin--Biology and Potential Cardiovascular Applications," Trends Cardiovasc. Med. 1(8):331-336 (1991).
Dittman and Majerus, "Structure and Function of Thrombomodulin: A Natural Anticoagulant," Blood 75(2):329-336 (1990).
Dreyfus et al., "Treatment of Homozygous Protein C Deficiency and Neonatal Purpura Fulminans with a Purified Protein C Concentrate," N. Engl. J. Med. 325(22):1565-1568 (1991).
Edgell, et al., "Permanent cell line expressing human factor VIII-related antigen established by hybridization," Proc. Natl. Acad. Sci. (USA) 80:3734-3737 (1983).
Engelman et al., "Identifying Nonpolar Transbilayer Helices in Amino Acid Sequences of Membrane Proteins," Annu. Rev. Biophys. Chem. 15:321-53 (1986). (1993).
Fukudome, et al., "The Endothelial Cell Protein C Receptor--Cell Surface Expression and Direct Ligand Binding by the Soluble Receptor," J. Biol. Chem. 271(29):17491-17498 (1996).
Fukudome and Esmon, "Molecular Cloning and Expression of Murine and Bovine Endothelial Cell Protein C/Activated Protein C Receptor (EPCR)--The Structural and Functional Conservation in Human, Bovine and Murine EPCR*," J. Biol. Chem. 270(10):5571-5577 (1995).
Fukudome and Esmon, "Identification, Cloning, and Regulation of a Novel Endothelial Cell Protein C/Activated Protein C Receptor*," J. Biol. Chem. 269(42):26486-26491 (1994).
Galvin, et al., "Reconstitution of Rabbit Thrombomodulin Into Phospholipid Vesicles," J. Biol. Chem. 262(5):2199-2205 (1987).
Gerson et al., "Severe Acquired Protein C Deficiency in Purpura Fulminans Associated with Disseminated Intravascular Coagulation: Treatment with Protein C Concentrate," Pediatrics 91(2):418-422 (1993).
Heaney, et al., "Membrane-associated and soluble granylocyte/macrophoage-colony -stimulating factor receptor .alpha. submits are independently regulated in HL-60 cells," Proc. Natl. Acad. Sci. U.S.A. 92:2365-2369 (1995).
Heaney, ML and DW Golde, "Soluble cytokine receptors," Blood 87(3):847-857 (1996).
Hofsteenge, et al., "Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors," Biochem. J. 237:243-251 (1986).
Horiuchi, et al., "Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated thourgh an alternative splicing mechanism," Eur. J. Immunol. 24:1945-1948 (1994).
Ishii and Majerus, "Thrombomodulin is Present in Human Plasma and Urine," J. Clin. Invest. 76:2178-2181 (1985).
Jackman, et al., "Human thrombomodulin gene is intron depleted: Nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control," Proc. Natl. Acad. Sci. (USA) 84:6425-6429 (1987).
Mathews, "Structure of a Nonadecapeptide of the Fifth EGF Domain of Thrombomodulin Complexed with Thrombin," Biochemistry 33:13547-13552 (1994).
Moore, et.al., "Tumor Necrosis Factor Leads to the Internalization and Degradation of Thrombosis from the Surface of Bovine Aortic Endothelial Cells in Culture," Blood 73(1):159-165 (1989).
Mullberg, et al., "The Soluble Human IL-6 Receptor," J. Immunol. 152:4958-4968 (1994).
Ohdama, et al., "Clinical Thrombomodulin in Wegener's Granulomatosis as an Indicator of Vascular Injuries," Chest 106:666-671 (1994).
Owen, et al., "The Conversion of Prothrombin to Thrombin," J. Biol. Chem. 249(2):594-605 (1974).
Parkinson, et al., "Stable Expression of a Secretable Deletion Mutant of Recombinant Human Thrombomodulin in Mammalian Cells," J. Biol. Chem. 265(21):12602-12610 (1990).
Quehenberger, et al., "Increased Levels of Activated Factor VII and Decreased Plasma Protein S Activity and Circulating Thrombomodulin During Use of Oral Contraceptives," Thromb. Haemost. 76:729-734 (1996).
Regan, et al., "The Endothelial Cell Protein C Receptor--Inhibition of Activated Protein C Anticoagulant Function without Modulation of Reaction with Proteinase Inhibitors*," J. Biol. Chem. 271(29):17499-17503 (1996).
Reitsma, et al., "Protein C Deficiency: A Database of Mutations, 1995 Update," Thromb. Haemost. 73:876-879 (1995).
Rezaie, et al., "Communication: Protein C Inhibitor Is a Potent Inhibitor of the Thrombin-Thrombomodulin Complex," J. Biol. Chem. 270(43):25336-25339 (1995).
Takahashi, et al., "Circulating Thrombomodulin As a Novel Endothelial Cell Marker: Comparison of Its Behavior with von Willebrand Factor and Tissue Type Plasminogen Activator," Am. J. Hematol. 41:32-39 (1992).
Takano, et al., "Plasma Thrombomodulin in Health and Diseases," Blood. 76(10):2024-2029 (1990).
Tanaka, et al., "Increased Thrombomodulin Values in Plasma of Diabetic Men with Microangiopathy," Clin. Chem. 37(2):269-272 (1991).
Taylor et al., "Protein C Prevents the Coagulopathic and Lethal Effects of Escherichia coli Infusion in the Baboon," J. Clin. Invest. 79:918-925 (1987).
Taylor et al., "C4b-Binding Protein Exacerbates the Host Response to Escherichia coli," Blood 78(2):357-363 (1991).
von Heijne, "A New Method for Predicting Signal Sequence Cleavage Sites," Nucleic Acids Res. 14(11):4683-4690 (1986).
Wada, et al., "Plasma Thrombomodulin as a Marker of Vascular Disorders in Thrombotic Thrombocytopenic Purpura and Disseminated Intravascular Coagulation," Am. J. Hematol. 39:20-24 (1992).
Wen, et al., "Human Thrombomodulin: Complete cDNA Sequence and Chromosome Localization of the Gene," Biochemistry 26:4350-4357 (1987).
Ye, et al., "The Fifth and Sixth Growth Factor-like Domains of Thrombomodulin Bind to the Anion-binding Exosite of Thrombin and Alter Its Specificity," J. Biol. Chem. 267(16):11023-11028 (1992).
Ye, et al., "The Active Site of Thrombin is Altered Upon Binding to Thrombomodulin--Two Distinct Structural Changes are Detected by Fluorescence, but only one Correlates with Protein C Activation," J. Biol. Chem., 266(34):23016-23021 (1991).

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