Enhancement of Factor VIII-von Willebrand Factor Ristocetin Cofactor Activity by Monoclonal Antibodies

V Hornsey; L R Micklem; M C McCann; K James; J Dawes; D B L McClelland; C V Prowse

doi:10.1055/s-0038-1657885

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1985; 54(02): 510-524
DOI: 10.1055/s-0038-1657885

Original Article

Schattauer GmbH Stuttgart

Enhancement of Factor VIII-von Willebrand Factor Ristocetin Cofactor Activity by Monoclonal Antibodies

V Hornsey

The Edinburgh and South-East Scotland Blood Transfusion Service, Royal Infirmary, Edinburgh, UK

,

L R Micklem

^*The Department of Surgery, Edinburgh University, Edinburgh, UK

,

M C McCann

^*The Department of Surgery, Edinburgh University, Edinburgh, UK

,

K James

^*The Department of Surgery, Edinburgh University, Edinburgh, UK

,

J Dawes

^**The MRC/SNBTS Blood Components Assay Group, Edinburgh, UK

,

D B L McClelland

The Edinburgh and South-East Scotland Blood Transfusion Service, Royal Infirmary, Edinburgh, UK

,

C V Prowse

The Edinburgh and South-East Scotland Blood Transfusion Service, Royal Infirmary, Edinburgh, UK

› Author Affiliations

Abstract

PDF Download

Summary

Five monoclonal antibodies to human von Willebrand factor were selected for characterization from 18 produced in murine hybridomas. All showed a high and specific affinity for human von Willebrand factor (vWf) but exhibited little if any crossreaction with sera from other species. The antibodies defined four epitopes on vWf, none of which were involved in platelet binding. Binding of two distinct antibodies at one of these epitopes was associated with enhancement of the rate of vWf-dependent platelet agglutination in the presence of ristocetin. This effect was more noticeable when cryosupernatant plasma was used in place of normal plasma as the source of vWf, and was not explicable simply in terms of antibody-induced cross-linking of vWf.

Keywords

Factor VIII - von Willebrand factor - Ristocetin cofactor - Monoclonal antibody

PDF (1126 kb)

References

References
1 Zimmerman TS, Ruggeri ZM, Fulcher CA. Factor VIII-von Willebrand factor. Prog. Haematol 1983; 13: 279-309
2 Sakariassen KS. The role of factor VIII-von Willebrand factor in platelet adherence to human artery subendothelium. Ph D Thesis. 1984. University of Utrecht;
3 Over J, Bouma BN, van Mourik JA, Sixma JJ. Heterogeneity of human factor VIII. I. Characterisation of factor VIII present in the supernatant of cryoprecipitate. J Lab Clin Med 1978; 91: 32-46
4 Sixma JJ, Sakariassen KS, Beeser-Visser NH, Ottenhof-Rovers M, Bolhuis PA. Adhesion of platelets to human artery sub-endothelium: effect of factor VIII von Willebrand factor of various multimeric compositions. Blood 1984; 63: 128-139
5 Andersen JC, Switzer MEP, McKee PA. Support of ristocetin-induced platelet aggregation by procoagulant inactive and plasmincleaved forms of human factor VIII-von Willebrand factor. Blood 1980; 55: 101-108
6 Martin SE, Marder VJ, Francis CW, Lofthus 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
7 Bradley LA, Franco EL, Reisner HM. Use of monoclonal antibodies in an enzyme immunoassay for factor VIII related antigen. Clin Chem 1984; 30: 87-92
8 Ogata K, Saito H, Ratnoff OD. The relationship of the properties of antihemophilic factor (factor VIII) that supports ristocetin-induced platelet agglutination (factor VIIIR: RC) and platelet retention by glass beads as demonstrated by a monoclonal antibody. Blood 1983; 61: 27-35
9 Goodall AH, Jarvis J, Chand S, Rawlings E, O’Brien DP, McCraw A, Hutton R, Tuddenham EGD. An immunoradiometric assay for human factor VIII-von Willebrand factor using monoclonal antibodies that define a functional epitope. Br J Haematol 1985; 59: 565-577
10 Fulcher CA, Zimmerman TS. Characterisation of the human factor VIII procoagulant protein with a heterologous precipitating antibody. Proc Natl Acad Sci USA 1982; 79: 1648-1652
11 Meyer D, Baumgartner HR, Edgington TS. Relative role of intramolecular loci in mediation of platelet adhesion to subendothelium. Br J Haematol 1984; 57: 609-620
12 Stel HV, Sakariassen KS, Scholte BJ, Veerman ECI, Van der Kwast TH, De Groot PG, Sixma JJ, Van Mourik JA. Characterisation of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to sub-endothelium. Blood 1984; 1408-1415
13 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
14 Schullek J, Jordan T, Montgomery R. Interaction of von Willebrand factor with human platelets in the plasma milieu. J Clin Invest 1984; 73: 421-428
15 Bowie EJW, Fass DN, Katzmann JA. Functional studies of von Willebrand factor using monoclonal antibodies. Blood 1983; 62: 146-151
16 Katzmann JA, Mujwid DK, Miller RS, Fass DN. Monoclonal antibodies to von Willebrand factor: reactivity with porcine and human antigens. Blood 1981; 58: 530-536
17 Kirby EP, Edgington TS. Characterisation of monoclonal antibodies to bovine von Willebrand factor. Thromb Haemostas 1983; 50: 191
18 Sola B, Avner P, Sultan Y, Jeanneau C, Maissoneuve P. Monoclonal antibodies against human factor VIII molecule neutralise antihemophilic factor and ristocetin cofactor activities. Proc Natl Acad Sci USA 1982; 79: 183-187
19 Booth WJ, Furby FH, Bennet MC, Castaldi PA. Factor VIII-von Willebrand factor has potent lectin activity. Biochem Biophys Res Comm 1984; 118: 495-501
20 Meyer D, Zimmermann TS, Obert B, Edgington TS. Hybridoma antibodies to human von Willebrand factor. I. Characterisation of seven clones. Br J Haematol 1984; 57: 597-608
21 Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 (Suppl. 124) 21-37
22 Macfarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson JA. A method for assaying von Willebrand factor (ristocetin cofactor). Thrombos Diathes Haemorrh 1975; 34: 306-308
23 Prowse CV, Sas G, Gader AMA, Cort JH, Cash JD. Specificity in the factor VIII response to vasopressin. Br J Haematol 1979; 41: 437-447
24 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
25 Salacinski PRR, McLean C, Sykes JEC, Clement-Jones CV, Lowry PJ. Iodination of proteins, glycoproteins and peptides using a solid phase oxidising agent (Iodogen). Anal Biochem 1981; 117: 996-1003
26 Kasper CK, Aledort L, Aronson D, Counts R, Edson JR, van Eys J, Franatoni J, Green D, Hampton J, Hilgartner M, Levine P, Lazerson J, McMillan C, Penner J, Shapiro S, Schulman NR. A more uniform measurement of factor VIII inhibitors. Thrombos Diathes Haemorrh 1975; 34: 869-872
27 Dawes J, James K, Micklem LR, Pepper DS, Prowse CV. Monoclonal antibodies directed against human thrombin and the thrombin-anti-thrombin complex. Thromb Res 1984; 36: 397-409
28 Kohn J, Wilchek M. A new approach (cyano-transfer) for cyanogen bromide activation of Sepharose at neutral pH, which yields activated resins free of interfering nitrogen derivatives. Biochem Biophys Res Comm 1982; 107: 878-884
29 Wright JF, Hunter WM. A convenient replacement for cyanogen bromide-activated solid phases in immunoradiometric assays. J Immunol Methods 1982; 48: 311-325
30 Hunter WM. Simplified solid phase radioimmunoassay without centrifugation. Acta Endocrinol 1977; 85 (Suppl. 212) 463
31 Griffin BD, Micklem LR, James K, McCann MC, Pepper DS. Production of monoclonal antibodies to human factor VIII coagulant protein. Hybridoma 1984; 3: 102
32 Hunter NR, Dawes J, MacGregor IR, Pepper DS. Quantitation by radioimmunoassay of thrombospondin synthesised and secreted by human endothelial cells. Thromb Haemostas 1985; 52: 288-291
33 Heiler G, Fass DN, Katzmann JA. Spontaneous platelet aggregating activity produced by von Willebrand factor modified by monoclonal antibodies. Circulation 1982; 66: 298
34 Melero JA, Gonzalez-Rodriquez J. Preparation of monoclonal antibodies against glycoprotein IIIa of human platelets: their effect on platelet aggregation. Eur J Biochem 1984; 141: 421-427
35 Coller BS. Biochemical and electrostatic considerations in primary platelet aggregation. Ann NY Acad Sci 1983; 416: 693-708
36 Senogles SE, Nelsestuen GL. Von Willebrand factor: a protein which binds at the cell surface interface between platelets. J Biol Chem 1983; 258: 12327-12333
37 Furlan M, Perret B, Beck EA. Von Willebrand activity of low molecular weight human factor VIII increases by binding to gold granules. Thromb Haemostas 1981; 45: 242-246