Characterisation of a Monoclonal Antibody to von Willebrand Factor as a Potent Inhibitor of Ristocetin-Mediated Platelet Interaction and Platelet Adhesion

Summary

We studied a murine monoclonal antibody (211 A6) to von Willebrand factor (vWF) with a view to investigating structure-relationship. of plasma vWF. The specificity of this antibody has been substantiated by ELISA tests and indirect immunofluorescence. It reacts with purified vWF, normal plasma but not with plasma or platelets from a severe von Willebrand’s disease patient. Monoclonal antibody 211 A6 is a potent inhibitor of ristocetin-induced platelet aggregation. The ¹²⁵I-FVIII/vWF binding to platelets in presence of ristocetin is totally inhibited by low 211 A6 concentrations. Thrombin-induced binding of vWF to platelets is not affected by 211 A6. The ability of this antibody to inhibit platelet adhesion to subendothelium and to collagen was investigated with a perfusion model. The complete inhibition of platelet adhesion by 211 A6 questions the similarity or the interrelationship in vWF domains involved in ristocetin-induced platelet functions and platelet adhesion.

Keywords

Monoclonal antibody - von Willebrand factor - Ristocetin cofactor - Platelet adhesion

• References

• 1 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of von Willebrand factor by human endothelial cells. Proc Natl Acad Sci USA 1974; 71: 1906-1909
• 2 Howard MA, Montgomery DC, Hardisty RM. Factor VIII-related antigen in platelets. Thromb Res 1974; 4: 617-624
• 3 Nachman RL, Levine R, Jaffe EA. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest 1977; 60: 914-921
• 4 Counts RB, Paskell SL, Elgee SK. Disulfide bonds and the quaternary structure of factor VIII/von Willebrand factor. J Clin Invest 1978; 62: 702-709
• 5 Hoyer LW, Shainoff JR. Factor VIII-related protein circulates in normal plasma as high molecular weight multimers. Blood 1980; 55: 1056-1059
• 6 Ruggeri ZM, Zimmermann TS. Variant von Willebrand’s disease characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325
• 7 Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, Walsh KA, Chopek MW, Sadler JE, Fujikawa K. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25: 3171-3184
• 8 Chopek MW, Girma JP, Fujikawa K, Davie EW, Titani K. Human von Willebrand factor: A multivalent protein composed of identical subunits. Biochemistry 1986; 25: 3146-3155
• 9 Sadler JE, Shelton-Inloes BB, Sorace JM, Harlan JM, Titani K, Davie EW. Cloning and characterisation of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci USA 1985; 82: 6394-6398
• 10 Shelton-Inloes BB, Titani K, Sadler JE. cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms. Biochemistry 1986; 25: 3164-3171
• 11 Weiss HJ, Turitto VT, Baumgartner HR. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate-dependent decrease of adhesion in von Willebrand’s disease and the Bernard Soulier syndrome. J Lab Clin Med 1978; 92: 750-764
• 12 Baumgartner HR, Tschopp TB, Meyer D. Shear. rate dependent inhibition of platelet adhesion and aggregation on collagenous surfaces by antibodies to human factor VIII/von Willebrand factor. Br J Haematol 1980; 44: 127-139
• 13 Kao KJ, Pizzo SV, McKee PA. Demonstration and characterization of specific binding sites for factor VIII/von Willebrand factor on human platelets. J Clin Invest 1979; 63: 656-664
• 14 Fujimoto T, Ohara S, Hawiger J. Thrombin-induced exposure and prostacyclin inhibition of the receptor for factor VIII/von Willebrand factor on human platelets. J Clin Invest 1982; 69: 1212-1222
• 15 Fujimoto T, Hawiger J. Adenosine diphosphate induces binding of von Willebrand factor to human platelets. Nature 1982; 297: 154-156
• 16 Di Minno G, Thiagarajan P, Perussia B, Martinez J, Shapiro S, Trinchieri G, Murphy S. Exposure of platelet fibrinogen-binding sites by collagen, arachidonic acid and ADP: inhibition by a monoclonal antibody to glycoprotein IIb-IIIa complex. Blood 1983; 61: 140-148
• 17 Goodall AH, Meyer D. Registry of monoclonal antibodies to factor VIII and von Willebrand factor. International committee on thrombosis and haemostasis. Thromb Haemostas 1985; 54: 878-891
• 18 Ogata K, Saito H, Ratnoff OD. The relationship of the properties of antihemophilic factor (factor VIII) that support ristocetin-induced platelet agglutination (factor VIIIR:RC) and platelet retention by glass beads as demonstrated by a monoclonal antibody. Blood 1983; 61: 27-35
• 19 Goodall AH, Jarvis J, Chand S, Rawlings E, O’Brien DP, McGraw A, Hutton R, Tuddenham E GD. An immunoradiometric assay for human factor VIII/von Willebrand factor (VIII:vWf) using a monoclonal antibody that defines a functional epitope. Br J Haematol 1985; 59: 565-577
• 20 Stel HV, Sakariassen KS, de Groot PG, Van Mourik JA, Sixma JJ. Von Willebrand factor in the vessel wall mediates platelet adherence. Blood 1985; 65: 85-90
• 21 Meyer D, Baumgartner HR, Edgington TS. Hybridoma antibodies to human von Willebrand factor II. Relative role of intramolecular loci in mediation of platelet adhesion to the subendothelium. Br J Haematol 1984; 57: 609-620
• 22 Stel HV, Sakariassen KS, Scholte BJ, Veerman EC, van der Kwast TH, de Groot PG, Sixma JJ, van Mourik JA. Characterization of 25 monoclonal antibodies to factor VIII - von Willebrand factor: Relationship between ristocetin induced platelet aggregation and platelet adherence to subendothelium. Blood 1984; 63: 1408-1415
• 23 Nokes TC, Mahmoud NA, Savidge GF, Goodall AH, Meyer D, Edgington TS, Hardisty RM. Von Willebrand factor has more than one binding site for platelets. Thromb Res 1984; 34: 361-366
• 24 Schullek J, Jordan J, Montgomery RR. Interaction of von Willebrand factor with human platelets in the plasma milieu. J Clin Invest 1984; 73: 421-428
• 25 Sola B, Avner P, Sultan Y, Jeanneau C, Maisonneuve P. Monoclonal antibodies against human factor VIII molecule neutralize antihemophilic factor and ristocetin cofactor activities. Proc Natl Acad Sci USA 1982; 79: 183-187
• 26 Croissant MP, van de Pol H, Lee HH, Allain JP. Characterization of four monoclonal antibodies to factor VIII coagulant protein and their use in immunopurification of factor VIII. Thromb Haemostas 1986; 56: 271-276
• 27 Ey PL, Prowse SJ, Jenkin CR. Isolation of pure IgG 1, IgG 2a and IgG 2b immunoglobulins from mouse serum using protein A-Sepharose. Immunochemistry 1978; 15: 429-436
• 28 Mazurier C, Parquet-Gernez A, Samor B, Goudemand M, Montreuil J. Etude de l’antigène lié au facteur VIII (FVIIIR:Ag). Purification par chromatographie d’immuno-affinité. C R Acad Sci Paris 1979; 288: 1431-1434
• 29 Katzman JA, Mujwid DK, Miller RS, Fass DN. Monoclonal antibodies to von Willebrand’s factor: Reactivity with porcine and human antigens. Blood 1981; 58: 530-536
• 30 Kasper CK. et al. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869-872
• 31 Sixma JJ, Sakariassen KS, Stel HV, Houdjik W PM, In der Maur DW, Hamer RJ, de Groot PG, van Mourik JA. Functional domains on von Willebrand factor: Recognition of discrete tryptic fragments by monoclonal antibodies that inhibit interaction of von Willebrand factor with platelets and with collagen. J Clin Invest 1984; 74: 736-744
• 32 Mazurier C, Parquet-Gernez A, Goudemand M. Dosage de l’antigène lié au facteur VIII par la technique ELISA. Intérêt dans l’étude de la maladie de Willebrand. Path Biol 1977; 25: 18-24
• 33 Patscheke H. Shape and functional properties of human platelets washed with acid citrate. Haemostasis 1981; 10: 14-27
• 34 Goudemand J, Mazurier C, Samor B, Bouquelet S, Montreuil J, Goudemand M. Effect of carbohydrate modifications of factor VIII/von Willebrand factor on binding to platelets. Thromb Haemostas 1985; 53: 390-395
• 35 Sakariassen KS, Bolhuis PA, Sixma JJ. Platelet adherence to subendothelium of human arteries in pulsatile and steady flow. Thromb Res 1980; 19: 547-559
• 36 Baumgartner HR. The role of blood flow in platelet adhesion, fibrin deposition and formation of mural thrombi. Microvasc Res 1973; 5: 167-179
• 37 Heyns A du P, Badenhorst PN, Pieters H, Lötter MG, Minnaar PC, Duyvené de Wit LJ, van Reenen OR, Retief FP. Preparation of a viable population of ¹¹¹Indium-labeled human blood platelets. Thromb Haemostas 1980; 42: 1473-1482
• 38 Jorieux S, Mazurier C, de Romeuf C, Goudemand M. Properties and interests of a monoclonal antibody to human von Willebrand factor (vWf). Bari International Conference on Factor VIII von Willebrand factor; 1985. June 10-15 Bari: (Abstr)
• 39 Sakariassen KS, Aarts P AM, de Groot PG, Houdjik W PM, Sixma JJ. A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their extracellular matrise and purified components. J Lab Clin Med 1983; 102: 522-535
• 40 Goodall AH, Jarvis J, Rawlings E, Tuddenham E GD. A specific immunoradiometric assay for VIII: vWF using monoclonal antibodies recognising a functional site on VIII:RAg. Thromb Haemost 1983; 50: 111
• 41 Martin SE, Marder VJ, Francis CW, Loftus LS, Barlow GH. Enzymatic degradation of the factor VIII/von Willebrand protein: a unique tryptic fragment with ristocetin cofactor activity. Blood 1980; 55: 848-858
• 42 Fujimura Y, Titani K, Holland LZ, Russell SR, Roberts JR, Elder JH, Ruggeri ZM, Zimmerman TS. Von Willebrand factor. A reduced and alkylated 52/48kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib. J Biol Chem 1986; 261: 381-385
• 43 Girma JP, Kalafatis M, Piétu G, Lavergne JM, Chopek MW, Edgington TS, Meyer D. Mapping of distinct von Willebrand factor domains interacting with platelet GPIb and GPIIb/IIIa and with collagen using monoclonal antibodies. Blood 1986; 67: 1356-1366
• 44 Girma JP, Kalafatis M, Piétu G, Lavergne JM, Edgington TS, Meyer D. Mapping of functional domains of human von Willebrand factor using monoclonal antibodies. Thromb Haemost 1985; 54: 59 (Abstr)