Download PDF
Thromb Haemost 1991; 66(05): 529-533
DOI: 10.1055/s-0038-1646454
Original Article
Schattauer GmbH Stuttgart

An Anti-Tissue Factor Monoclonal Antibody which Inhibits TF Vlla Complex Is a Potent Anticoagulant in Plasma

Wolfram Ruf
The Vascular Biology Group, Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA, USA
,
Thomas S Edgington
The Vascular Biology Group, Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA, USA
› Author Affiliations
Further Information

Publication History

Received 17 August 1990

Accepted 24 April 1991

Publication Date:
25 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Tissue factor (TF) functions as the receptor and cofactor for factor VIIa (VIIa) to form a proteolytically active TFVIIa complex on cell surfaces. We here demonstrate that most MAbs against human TF were poor inhibitors of TF function in plasma and that they inhibited preformed TF-VIIa complex at a slow rate which was dependent on dissociation of VIIa from the cell surface TF. An exception was defined by one MAb (TF8-5G9) which was an effective immediate anticoagulant in plasma. Binding of TF8-5G9 to TF-VIIa inhibited catalytic function prior to dissociation of the TF-VIIa complex. This analysis thus establishes two distinct mechanisms by which MAbs interfere with TF function. The MAb TF8-5G9 introduces a therapeutic principle for rapid arrest of inappropriate triggering of coagulation by TF as well as the TF-VIIa complex in vivo.

 

  • References

  • 1 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Am J Pathol 1989; 134: 1087-97
    PubMedGoogle Scholar
  • 2 Gregory SA, Morrissey JH, Edgington TS. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 1989; 9: 2752-5
    CrossrefPubMedGoogle Scholar
  • 3 Scarpati EM, Sadler JE. Regulation of endothelial cell coagulant properties. Modulation of tissue factor, plasminogen activator inhibitors, and thrombomodulin by phorbol 12-myristate 13-acetate and tumor necrosis factor. J Biol Chem 1989; 264: 20705-13
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 5 Nawroth PP, Handley DA, Esmon CT, Stern DM. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 1986; 83: 3460-4
    CrossrefPubMedGoogle Scholar
  • 6 Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Med Exp 1986; 163: 740-5
    PubMedGoogle Scholar
  • 7 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: Characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 1986; 83: 4533-7
    CrossrefPubMedGoogle Scholar
  • 8 Bevilacqua MP, Pober JS, Majeau GR, Cotran RS, Gimbrone 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
    CrossrefPubMedGoogle Scholar
  • 9 Edwards RL, Rickles FR, Bobrove AM. Mononuclear cell tissue factor: Cell of origin and requirements for activation. Blood 1979; 54: 359-70
    PubMedGoogle Scholar
  • 10 Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86: 2839-43
    CrossrefPubMedGoogle Scholar
  • 11 Edgington TS, Taylor F, Chang A, Ruf W, Blick K, Mackman N, Morrissey JH. Tissue factor: Molecular biology and significance in the pathophysiology of gram-negative septic shock. In: Microbiological, Chemotherapeutical and Immunological Problems in High Risk Patients.. Garaci E, Renzini G, Filadoro F, Goldstein AL, Verhoef J. (eds) Raven Press, New York: 1989. pp 29-37
    Google Scholar
  • 12 Warr TA, Rao LVM, Rapaport SI. Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: Effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. Blood 1990; 75: 1481-9
    PubMedGoogle Scholar
  • 13 Broze GJ. Binding of human factor VII and VIIa to monocytes. J Clin Invest 1982; 70: 526-35
    CrossrefPubMedGoogle Scholar
  • 14 Ploplis VA, Edgington TS, Fair DS. Initiation of the extrinsic pathway of coagulation. Association of factor VIIa with a cell line expressing tissue factor. J Biol Chem 1987; 262: 9503-8
    PubMedGoogle Scholar
  • 15 Fair DS, MacDonald MJ. Cooperative interaction between factor VII and cell surface-expressed tissue factor. J Biol Chem 1987; 262: 11692-8
    PubMedGoogle Scholar
  • 16 Bach R, Gentry R, Nemerson Y. Factor VII binding to tissue factor in reconstituted phospholipid vesicles: Induction of cooperativity by phosphatidylserine. Biochemistry 1986; 25: 4007-20
    CrossrefPubMedGoogle Scholar
  • 17 Osterud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: Additional pathway for initiating blood coagulation. Proc Natl Acad Sci USA 1977; 74: 5260-4
    CrossrefPubMedGoogle Scholar
  • 18 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
    PubMedGoogle Scholar
  • 19 Silverberg SA, Nemerson Y, Zur M. Kinetics of the activation of bovine coagulation factor X by components of the extrinsic pathway. Kinetic behavior of two-chain factor VII in the presence and absence of tissue factor. J Biol Chem 1977; 252: 8481-8
    PubMedGoogle Scholar
  • 20 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
    CrossrefPubMedGoogle Scholar
  • 21 Taylor FB, Chang A, Ruf W, Morrissey JH, Hinshaw LB, Catlett R, Blick K, Edgington TS. Lethal E.coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-34
    PubMedGoogle Scholar
  • 22 Fair DS. Quantitation of factor VII in the plasma of normal and warfarin-treated individuals by radioimmunoassay. Blood 1983; 62: 784-91
    PubMedGoogle Scholar
  • 23 Burri BJ, Edgington TS, Fair DS. Molecular interaction of the intrinsic activation complex of coagulation: binding of native and activated human factors IX and X to defined phospholipid vesicles. Biochim Biophys Acta 1987; 923: 176-86
    CrossrefPubMedGoogle Scholar
  • 24 Fair DS, Plow EF, Edgington TS. Combined functional and immunochemical analysis of normal and abnormal human factor X. J Clin Invest 1979; 64: 884-94
    CrossrefPubMedGoogle Scholar
  • 25 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5
    CrossrefPubMedGoogle Scholar
  • 26 Morrissey JH, Revak D, Tejada P, Fair DS, Edgington TS. Resolution of monomelic and heterodimeric forms of tissue factor, the high-affinity cellular receptor for factor VII. Thromb Res 1988; 50: 481-93
    CrossrefPubMedGoogle Scholar
  • 27 Carson SD, Konigsberg WH. Cadmium increases tissue factor (coagulation factor III) activity by facilitating its reassociation with lipids. Science 1980; 208: 307-9
    CrossrefPubMedGoogle Scholar
  • 28 Morrissey JH, Fair DS, Edgington TS. Monoclonal antibody analysis of purified and cell-associated tissue factor. Thromb Res 1988; 52: 247-61
    CrossrefPubMedGoogle Scholar
  • 29 Coulter A, Harris R. Simplified preparation of rabbit Fab fragments. J Immunol Methods 1983; 59: 199-203
    CrossrefPubMedGoogle Scholar
  • 30 Goding JW. Use of staphylococcal protein A as an immunological reagent. J Immunol Methods 1978; 20: 241-53
    CrossrefPubMedGoogle Scholar
  • 31 Drake TA, Ruf W, Morrissey JH, Edgington TS. Functional tissue factor is entirely cell surface expressed on lipopolysaccharide-stimulated human blood monocytes and a constitutively tissue factor-producing neoplastic cell line. J Cell Biol 1989; 109: 389-95
    CrossrefPubMedGoogle Scholar
  • 32 Brooks SPJ, Suelter CH. Estimating enzyme kinetic parameters: A computer program for linear regression and non-parametric analysis. Int J Bio-Med Comput 1986; 19: 89-99
    CrossrefPubMedGoogle Scholar
  • 33 Wilkinson GN. Statistical estimations in enzyme kinetics. Biochem J 1961; 80: 324-32
    CrossrefPubMedGoogle Scholar
  • 34 Bom VJJ, Bertina RM. The contributions of Ca2+, phospholipids and tissue-factor apoprotein to the activation of human blood-coagulation factor X by activated factor VII. Biochem J 1990; 265: 327-36
    CrossrefPubMedGoogle Scholar
  • 35 Carson SD, Bach R, Carson SM. Monoclonal antibodies against bovine tissue factor, which block interaction with factor VIIa. Blood 1985; 66: 152-6
    PubMedGoogle Scholar
  • 36 Seligsohn U, Kasper CK, Osterud B, Rapaport SI. Activated factor VII: Presence in factor IX concentrates and persistence in the circulation after infusion. Blood 1979; 53: 828-37
    PubMedGoogle Scholar
  • 37 Sandset PM, Warn-Cramer BJ, Rao LVM, Maki SL, Rapaport SI. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: Evidence supporting a physiologic role for EPI as a natural anticoagulant. Proc Natl Acad Sci USA 1991; 88: 708-12
    CrossrefPubMedGoogle Scholar
  • 38 Warr TA, Rao LVM, Rapaport SI. Human plasma extrinsic pathway inhibitor activity: II. Plasma levels in disseminated intravascular coagulation and hepatocellular disease. Blood 1989; 74: 994-8
    PubMedGoogle Scholar
  • 39 Broze Jr GJ, Girard TJ, Novotny WF. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 1990; 29: 7539-46
    CrossrefPubMedGoogle Scholar
  • 40 Girard TJ, MacPhail LA, Likert KM, Novotny WF, Miletich JP, Broze J. Inhibition of factor VIIa-tissue factor coagulation activity by a hybrid protein. Science 1990; 248: 1421-4
    CrossrefPubMedGoogle Scholar
  • 41 Pedersen AH, Nordfang O, Norris F, Wiberg FC, Christensen PM, Moeller KB, Meidahl-Pedersen J, Beck TC, Norris K, Hedner U, Kisiel W. Recombinant human extrinsic pathway inhibitor. Production, isolation, and characterization of its inhibitory activity on tissue factor-initiated coagulation reactions. J Biol Chem 1990; 265: 16786-93
    PubMedGoogle Scholar
  • 42 Kondo S, Noguchi M, Funakoshi T, Fujikawa K, Kisiel W. Inhibition of human factor VIIa-tissue factor activity by placental anticoagulant protein. Thromb Res 1987; 48: 449-59
    CrossrefPubMedGoogle Scholar
  • 43 Gramzinski RA, Broze Jr GJ, Carson SD. Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II. Blood 1989; 73: 983-9
    PubMedGoogle Scholar
  • 44 Ruf W, Rehemtulla A, Morrissey JH, Edgington TS. Phospholipid independent and dependent interactions required for tissue factor receptor and cofactor function. J Biol Chem 1991; 266: 2158-66
    PubMedGoogle Scholar