Extrinsic Activation of Human Coagulation Factors IX and X on the Endothelial Surface

Victor J J Bom; Victor W M van Hinsbergh; Hanneke H Reinalda-Poot; Ramon W Mohanlal; Rogier M Bertina

doi:10.1055/s-0038-1646408

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1991; 66(03): 283-291
DOI: 10.1055/s-0038-1646408

Review Article

Schattauer GmbH Stuttgart

Extrinsic Activation of Human Coagulation Factors IX and X on the Endothelial Surface

Authors

Victor J J Bom

The Division of Haemostasis and Thrombosis, University Hospital, Groningen, the Haemostasis and Thrombosis Research Unit, University Hospital, Leiden and the Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
Victor W M van Hinsbergh

The Division of Haemostasis and Thrombosis, University Hospital, Groningen, the Haemostasis and Thrombosis Research Unit, University Hospital, Leiden and the Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
Hanneke H Reinalda-Poot

The Division of Haemostasis and Thrombosis, University Hospital, Groningen, the Haemostasis and Thrombosis Research Unit, University Hospital, Leiden and the Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
Ramon W Mohanlal

The Division of Haemostasis and Thrombosis, University Hospital, Groningen, the Haemostasis and Thrombosis Research Unit, University Hospital, Leiden and the Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
Rogier M Bertina

The Division of Haemostasis and Thrombosis, University Hospital, Groningen, the Haemostasis and Thrombosis Research Unit, University Hospital, Leiden and the Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands

Abstract

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Summary

In previous kinetic studies, the catalytic efficiency of the activation of human coagulation factors IX and X by factor VIIa in the presence of purified tissue factor apoprotein was found to be essentially equal. These activation reactions were now studied on the surface of human umbilical vein endothelial cells. The cells were stimulated with endotoxin to express tissue factor. This tissue factor activity was saturable with factor VIIa and could be inhibited by rabbit antibodies against human tissue factor apoprotein. Only stimulated cells supported factor VIIa activity. No difference in the reactivity of factor VII and VIIa was observed in the presence of factor X, due to rapid feedback activation of factor VII by factor Xa. However, the activation of factor IX by factor VII shows a 10 min lag-phase, which reflects that the activation of factor VII by factor IXa is a less efficient process. The kinetic parameters for the factor VIIa dependent activation of factor IX and factor X on the endothelial surface were: Km 0.09 εM, Vmax 0.13 pmol/min, and Km 0.071 εM, Vmax 0.41 pmol/min, respectively. The same ratio between the Vmax for factor X and factor IX activation was observed as in a cell free system. However, the Km of factor IX was 4-fold higher on the endothelial surface than in the cell free system. Together, these kinetic parameters will favour factor X activation 5-fold over factor IX activation at physiological concentrations of these proteins.

The activation of factor X by factor VIIa on the endothelial surface was characterized by a short lag-phase, which was absent in factor IX activation. Further, both the activation of factor X and factor IX were down regulated by factor Xa.

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References

References
1 Gimbrone Jr MA. (ed) Vascular Endothelium in Hemostasis and Thrombosis. Churchill Livingstone, London: 1986
2 Muller-Berghaus G. Septicemia and the vessel wall. In: Thrombosis and Haemostasis 1987.. Verstraete M, Vermylen J, Lijnen HR, Arnout J. (eds) International Society on Thrombosis and Haemostasis and Leuven University Press, Leuven: 1987. pp 619-71
3 Colucci M, Balconi G, Lorenzet R, Pietra A, Locati D, Donati MB, Sememaro N. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-6
4 Brox JH, Osterud B, Bjorklid E, Fenton JW. Production and availability of thromboplastin in endothelial cells: the effects of thrombin, endotoxin and platelets. Br J Haematol 1984; 57: 239-46
5 Stern DM, Nawroth PP, Handley D, Kisiel W. An endothelial cell-dependent pathway of coagulation. Proc Natl Acad Sci USA 1985; 82: 2523-7
6 Lyberg T, Galdal KS, Evensen SA, Prydz H. Cellular cooperation in endothelial cell thromboplastin synthesis. Br J Haematol 1983; 53: 85-95
7 Nawroth PP, Stern DM, Kisiel W, Bach R. Cellular requirements for tissue factor generation by bovine aortic endothelial cells in culture. Thromb Res 1985; 40: 677-91
8 Bevilacqua MP, Pober JS, Majeau GR, Cotran RS, Gimbrone Jr MA. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984; 160: 618-23
9 Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740-5
10 Stern DM, Drillings M, Kisiel W, Nawroth PP, Nossel HL, LaGamma KS. Activation of factor IX bound to cultured bovine aortic endothelial cells. Proc Natl Acad Sci USA 1984; 81: 913-7
11 Galdal KS, Lyberg T, Evensen SA, Nilsen E, Prydz H. Thrombin induces thromboplastin synthesis in cultured vascular endothelial cells. Thromb Haemostas 1985; 54: 373-6
12 Jesty J, Silverberg SA. Kinetics of the tissue factor-dependent activation of coagulation factors IX and X in a bovine plasma system. J Biol Chem 1979; 254: 12337-45
13 Osterud B, Rapaport SI. Activation of ¹²⁵I-factor IX and ¹²⁵I-factor X: effect of tissue factor and factor VII, factor Xa and thrombin. Scand J Haematol 1980; 24: 213-26
14 Broze Jr GJ. Binding of human factor VII and VIIa to monocytes. J Clin Invest 1982; 70: 526-35
15 Zur M, Radcliffe RD, Oberdick J, Nemerson Y. The dual role of factor VII in blood coagulation. Initiation and inhibition of a proteolytic system by a zymogen. J Biol Chem 1982; 257: 5623-31
16 Morrison SA, Jesty J. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. Blood 1984; 63: 1338-47
17 Warn-Cramer BJ, Bajaj SP. Intrinsic versus extrinsic coagulation. Kinetic considerations. Biochem J 1986; 239: 757-62
18 Bom VJJ, Ram IE, Alderkamp GHJ, Reinalda-Poot JH, Bertina RM. Application of factor VH-sepharose affinity chromatography in the purification of human tissue factor apoprotein. Thromb Res 1986; 42: 635-43
19 Van Dieijen G, Tans G, Rosing J, Hemker HC. The role of phospholipid and factor VIIIa in the activation of bovine factor X. J Biol Chem 1981; 256: 3433-42
20 Hultin MB. Role of human factor VIII in factor X activation. J Clin Invest 1982; 69: 950-8
21 Mertens K, Van Wijngaarden A, Bertina RM. The role of factor VIII in the activation of human blood coagulation factor X by activated factor IX. Thromb Haemostas 1985; 54: 654-60
22 Jackson CM. The biochemistry of prothrombin activation. In: Haemostasis and Thrombosis.. Bloom AL, Thomas DP. (eds) 2nd ed. Churchill Livingstone, London: 1987. pp 165-91
23 Bloom AL. Inherited disorders of blood coagulation. In: Haemostasis and Thrombosis.. Bloom AL, Thomas DP. (eds) 2nd ed. Churchill Livingstone, London: 1987. pp 393-436
24 Van den Besselaar AMHP, Ram IE, Alderkamp GHJ, Bertina RM. The role of factor IX in tissue thromboplastin induced coagulation. Thromb Haemostas 1982; 48: 54-8
25 Biggs R, Nossel HL. Tissue extract and the contact reaction in blood coagulation. Thromb Diath Haemorrh 1961; 6: 1-14
26 Marlar RA, Kleiss AJ, Griffin JH. An alternative extrinsic pathway of human blood coagulation. Blood 1982; 60: 1353-8
27 Rodgers GM, Greenberg CS, Shuman MA. Characterization of the effects of cultured vascular cells on the activation of blood coagulation. Blood 1983; 61: 1155-62
28 Almus FE, Rao LVM, Rapaport SI. Functional properties of factor VIIa/tissue factor formed with purified tissue factor and with tissue factor expressed on cultured endothelial cells. Thromb Haemostas 1989; 62: 1067-73
29 Stern DM, Drillings M, Nossel HL, Hurlet-Jensen A, LaGamma KS, Owen J. Binding of factors IX and IXa to cultured vascular endothelial cells. Proc Natl Acad Sci USA 1983; 80: 4119-23
30 Rodgers GM, Shuman MA. Prothrombin is activated on vascular endothelial cells by factor Xa and calcium. Proc Natl Acad Sci USA 1983; 80: 7001-5
31 Cerveny TJ, Fass DN, Mann KG. Synthesis of coagulation factor V by cultured aortic endothelium. Blood 1984; 63: 1467-74
32 Nawroth PP, Handley D, Stern DM. The multiple levels of endothelial cell-coagulation factor interactions. Clin Haematol 1986; 15: 293-321
33 Varadi K, Elodi S. Formations and functions of the factor IXa–VIII complex on the surface endothelial cells. Blood 1987; 69: 442-5
34 Bom VJJ, Bertina RM. The contributions of calcium, phospholipids and tissue factor apoprotein to the activation of human blood coagulation factor X by activated factor VII. Biochem J 1990; 265: 327-36
35 Bom VJJ, Reinalda-Poot JH, Cupers R, Bertina RM. Extrinsic activation of human blood coagulation factor IX and X. Thromb Haemostas 1990; 63: 224-30
36 Maciag T, Cerundolo J, Ilsley S, Kelly PR, Forand R. An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization. Proc Natl Acad Sci USA, 1979; 76: 5674-8
37 Bom VJJ, Van Tilburg NH, Krommenhoek-Van Es C, Bertina RM. Immunoradiometric assay for human coagulation factor VII using polyclonal antibodies against the Ca(II)-dependent and Ca(II)-independent conformation. Thromb Haemostas 1986; 56: 343-8
38 Mertens K, Cupers R, Van Wijngaarden A, Bertina RM. Binding of human blood-coagulation factors IXa and X to phospholipid membranes. Biochem J 1984; 223: 599-605
39 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins: identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-56
40 Van Hinsbergh VWM, Havekes L, Emeis JJ, Van Corven E, Scheffer M. Low density lipoprotein metabolism by endothelial cells from human umbilical cord arteries and veins. Arteriosclerosis 1983; 3: 547-59
41 Fair DS, MacDonald MJ. Cooperative interaction between factor VII and cell surface-expressed tissue factor. J Biol Chem 1987; 262: 11692-8
42 Rogers GM, Broze GJ, Shuman MA. The numbers of receptors for factor VII correlates with the ability of cultured cells to initiate coagulation. Blood 1984; 63: 434-8
43 Nemerson Y, Gentry R. An ordered addition, essential activation model of the tissue factor pathway of coagulation: evidence for a conformational cage. Biochemistry 1986; 25: 4020-33
44 Bom VJJ, Reinalda-Poot JH, Poort SR, Cupers R, Bertina RM. An immuno-radiometric assay of activated human coagulation factor IX. Thromb Res 1987; 45: 661-7
45 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54
46 DiScipio RG, Hermodson MA, Yates SG, Davie EW. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor) and protein S. Biochemistry 1977; 16: 698-706
47 Weber K, Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem 1969; 244: 4406-12
48 Stern DM, Nawroth PP, Kisiel W, Handley M, Bartos J. A coagulation pathway on bovine aortic segments leading to generation of factor Xa and thrombin. J Clin Invest 1984; 74: 1910-21
49 McGee MP, Wallin R, Wheeler FB, Rothbergen H. Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: A kinetic study. Blood 1989; 74: 1583-90
50 Broze Jr GJ, Majerus PW. Purification and properties of human coagulation factor VII. J Biol Chem 1980; 255: 1242-7
51 Masys DR, Bajaj SP, Rapaport SI. Activation of human factor VII by activated factors IX and X. Blood 1982; 60: 1143-50
52 Rao LVM, Rapaport SI, Bajaj SP. Activation of human factor VII in the initiation of tissue factor-dependent coagulation. Blood 1986; 68: 685-91
53 Di Scipio RG, Kurachi K, Davie EW. Activation of human factor IX (Christmas factor). J Clin Invest 1978; 61: 1528-38
54 Anson DS, Choo KH, Rees DJG, Gianelli F, Gould K, Huddlestone JA, Brownlee GG. The gene structure of human antihaemophilic factor IX. EMBO J 1984; 3: 1053-60
55 Leytus SP, Chung DW, Kisiel W, Kurachi K, Davie EW. Characterization of a cDNA coding for human factor X. Proc Natl Acad Sci USA 1984; 81: 3699-702
56 Rao LVM, Rapaport SI, Lorenzi M. Enhancement by human umbilical vein endothelial cells of factor Xa-catalyzed activation of factor VII. Blood 1988; 71: 791-6
57 Radcliffe R, Nemerson Y. Activation and control of factor VII by activated factor X and thrombin. Isolation and characterization of a single chain form of factor VII. J Biol Chem 1975; 250: 388-95
58 Zur M, Nemerson Y. Kinetics of factor IX activation via the extrinsic pathway. Dependence of Km on tissue factor. J Biol Chem 1980; 255: 5703-7
59 Radcliffe R, Nemerson Y. Mechanism of activation of bovine factor VII. Products of cleavage by factor Xa. J Biol Chem 1976; 251: 4797-802
60 Hubbard AR, Jennings CA. Inhibition of tissue thromboplastinmediated blood coagulation. Thromb Res 1986; 42: 489-98
61 Sanders NL, Bajaj SP, Zivelin A, Rapaport SI. Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component. Blood 1985; 66: 204-412
62 Rao LVM, Rapaport SI. Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood 1987; 69: 645-51
63 Warn-Cramer BJ, Maki SL, Zivelin A, Rapaport SI. Partial purification and characterization of extrinsic pathway inhibitor (the factor Xa-dependent plasma inhibitor of factor VIIa/tissue factor). Thromb Res 1987; 48: 11-22
64 Broze Jr GJ, Miletich JP. Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells. Proc Natl Acad Sci USA 1987; 84: 1886-90
65 Bajaj MS, Rana SV, Wysolmerski RB, Bajaj SP. Inhibitor of the factor VIIa-tissue factor complex is reduced in patients with disseminated intravascular coagulation but not in patients with severe hepatocellular disease. J Clin Invest 1987; 79: 1874-8
66 Nemerson Y, Repke D. Tissue factor accelerates the activation of coagulation factor VII: the role of a bifunctional coagulation cofactor. Thromb Res 1985; 40: 351-8
67 Mertens K, Bertina RM. Activation of human coagulation factor VIII by activated factor X, the common product of the intrinsic and the extrinsic pathway of blood coagulation. Thromb Haemostas 1982; 47: 96-100
68 Elodi S, Varadi K, Voros E. Kinetics of formation of factor IXa-factor VIII complex on the surface of platelets. Thromb Res 1981; 21: 695-700
69 Rosing J, Van Rijn JLML, Bevers EM, Van Dieijen G, Comfurius P, Zwaal RFA. The role of activated platelets in prothrombin and factor X activation. Blood 1985; 65: 319-32
70 Maynard JR, Dreyer BE, Stemerman ME, Pitlick FA. Tissue factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts. Blood 1977; 50: 387-96