Download PDF
Thromb Haemost 1992; 68(06): 707-713
DOI: 10.1055/s-0038-1646348
Original Article
Schattauer GmbH Stuttgart

Aurin Tricarboxylic Acid Inhibits Platelet Adhesion to Collagen by Binding to the 509-695 Disulphide Loop of von Willebrand Factor and Competing with Glycoprotein Ib

J P Girma
1   Inserm U.143, Hôpital de Bicêtre, Paris, France
,
E Fressinaud
2   Centre Départemental de Transfusion, Angers, France
,
O Christophe
1   Inserm U.143, Hôpital de Bicêtre, Paris, France
,
C Rouault
1   Inserm U.143, Hôpital de Bicêtre, Paris, France
,
B Obert
1   Inserm U.143, Hôpital de Bicêtre, Paris, France
,
Y Takahashi
3   Department of Pediatrics, Nara Medical College, Nara, Japan
,
D Meyer
1   Inserm U.143, Hôpital de Bicêtre, Paris, France
› Author Affiliations
Further Information

Publication History

Received 24 January 1992

Accepted after revision 22 July 1992

Publication Date:
04 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Aurin tricarboxylic acid (ATA) is known to inhibit ristocetin-induced platelet agglutination but not arachidonic acid-, epinephrine- or ADP-induced aggregation. Its capacity to abolish human von Willebrand factor (vWF)-platelet interactions was further investigated by measurement of platelet adhesion to collagen, platelet agglutination tests and binding studies. In flowing blood using parallel-plate perfusion chambers and human collagen, ATA inhibited platelet adhesion to completion in a dose-dependent manner only at the highest shear rate tested (2,600 s–1). It was without effect at 100 and 650 s–1. ATA completely abolished vWF-dependent platelet agglutination induced by ristocetin, botrocetin and asialo-vWF, respectively. 125I-vWF binding to ristocetin- and botrocetin-treated platelets, to heparin and to sulfatides as well as 125I-botrocetin binding to vWF was competitively inhibited by ATA. By contrast, binding of 125I-vWF to collagen was not affected. To further localize the domain of vWF interacting with ATA, experiments of inhibition of binding of selected 125I-monoclonal antibodies (MoAbs) to immobilized vWF by ATA were performed. Our data led to the conclusion that: 1) the interaction of ATA with vWF involves sequences of the A1 disulphide loop of vWF (residues 509–695) and close epitopes which interact with GPIb and 2) the inhibition of platelet adhesion by ATA occurs only at a high shear rate where vWF is known to play a key role. Thus ATA, which blocks the vWF/GPIb pathway by interfering with vWF and not with platelets, is a potential tool in preventing the early stages of thrombosis.

 

  • REFERENCES

  • 1 Baruch D, Bahnak B, Girma JP, Meyer D. von Willebrand Factor and platelet function. In: Platelet Disorders. Caen J. (ed) Bailliere’s Clin Haematol: 1989. pp 627-672
    Google Scholar
  • 2 Kalafatis M, Takahashi Y, Girma JP, Meyer D. Localization of a collagen-interactive domain of human von Willebrand Factor between amino acid residues Gly 911 and Glu 1,365. Blood 1987; 70: 1577-1583
    PubMedGoogle Scholar
  • 3 Pareti FI, Fujimura Y, Dent JA, Holland LZ, Zimmerman TS, Ruggeri ZM. Isolation and characterization of a collagen binding domain in human von Willebrand Factor. J Biol Chem 1986; 261: 15310-15315
    PubMedGoogle Scholar
  • 4 Pareti FJ, Niiya K, McPherson JM, Ruggeri ZM. Isolation and characterization of two domains of human von Willebrand Factor that interact with fibrillar collagen types I and III. J Biol Chem 1987; 262: 13835-13841
    PubMedGoogle Scholar
  • 5 Mohri H, Yoshioka A, Zimmerman TS, Ruggeri ZM. Isolation of von Willebrand Factor domain interacting with glycoprotein lb, heparin and collagen and characterization of its three distinct functional sites. J Biol Chem 1989; 264: 17361-17367
    PubMedGoogle Scholar
  • 6 De Groot PG, Ottentof-Rovers M, van Mourik JA, Sixma JJ. Evidence that the primary binding site of von Willebrand Factor that mediates platelet adhesion on subendothelium is not collagen. J Clin Invest 1988; 82: 65-73
    CrossrefPubMedGoogle Scholar
  • 7 Christophe O, Obert B, Meyer D, Girma JP. The binding of von Willebrand Factor to sulfatides is distinct from those interacting with glycoprotein lb, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673. Blood 1991; 78: 2310-2317
    PubMedGoogle Scholar
  • 8 Berndt MC, Booth WJ, Andrews RK, Castaldi PA. Definition of von Willebrand Factor (vWF)-GPIb-IX complex interaction using vWF peptides. Thromb Haemostas 1991; 65: 748 (Abstract)
    PubMedGoogle Scholar
  • 9 Fretto LJ, Fowler WE, McCaslin DR, Erickson HP, McKee PA. Substructure of human von Willebrand Factor: proteolysis by V8 and characterization of two functional domains. J Biol Chem 1986; 261: 15679-15689
    PubMedGoogle Scholar
  • 10 Sobel M, Soler DF, Kermode JC, Harris RB. Localization and characterization of a heparin binding domain peptide of human von Willebrand Factor. J Biol Chem 1992; 267: 8857-8862
    PubMedGoogle Scholar
  • 11 Mohri H, Fujimura Y, Shima M, Yosohioka A, Houghten RA, Ruggeri ZM, Zimmermann TS. Structure of von Willebrand Factor domain interacting with glycoprotein lb. J Biol Chem 1988; 263: 17901-17904
    PubMedGoogle Scholar
  • 12 Girma JP, Kalafatis M, Pietu 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
    PubMedGoogle Scholar
  • 13 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
    PubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 Bolhuis PA, Sakariassen KS, Sander HJ, Bouma BN, Sixma JJ. Binding of Factor VIII/von Willebrand Factor to subendothelium precedes platelet adhesion and enhances platelet spreading. J Lab Clin Med 1981; 97: 568-576
    PubMedGoogle Scholar
  • 16 Coller BS, Peerschke EI, Scudder LE, Sullivan CA. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand Factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand Factor. Blood 1983; 61: 099-111
    PubMedGoogle Scholar
  • 17 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Heliums JD. Involvement of large plasma von Willebrand Factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986; 78: 1456-1461
    CrossrefPubMedGoogle Scholar
  • 18 Howard MA, Perkin J, Salem HH, Firkin BG. The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane. Br J Haematol 1984; 57: 25-35
    CrossrefPubMedGoogle Scholar
  • 19 Sugimoto M, Mohri H, McClintock RA, Ruggeri ZM. Identification of discontinuous von Willebrand Factor sequences involved in complex formation with botrocetin. J Biol Chem 1991; 266: 18172-18178
    PubMedGoogle Scholar
  • 20 De Marco L, Girolami A, Russel S, Ruggeri ZM. Interaction of asialo von Willebrand Factor with glycoprotein lb induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation. J Clin Invest 1985; 75: 1198-1203
    CrossrefPubMedGoogle Scholar
  • 21 Phillips MD, Moake JL, Nolasco L, Turner N. Aurin tricarboxylic acid: a novel inhibitor of the association of von Willebrand Factor and platelets. Blood 1988; 72: 1898-1903
    PubMedGoogle Scholar
  • 22 Strony J, Phillips M, Brands D, Moake J, Adelman B. Aurintricar-boxylic acid in a canine model of coronary artery thrombosis. Circulation 1990; 81: 1106-1114
    CrossrefPubMedGoogle Scholar
  • 23 Weinstein M, Vosburg E, Phillips M, Turner N, Chute-Rose L, Moake J. Isolation from commercial aurintricarboxylic acid of the most effective polymeric inhibitors of von Willebrand Factor interaction with platelet glycoprotein lb. Comparison with other polyanionic and polyaromatic polymers. Blood 1991; 78: 2291-2298
    PubMedGoogle Scholar
  • 24 Sakariassen KS, Aarts PAM, de Groot PhG, Houdijk WPM, Sixma JJ. A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their extracellular matrix and purified components. J Lab Clin Med 1983; 102: 522-535
    PubMedGoogle Scholar
  • 25 Sakariassen KS, Joss R, Muggli R, Kuhn H, Tschopp TB, Sage H, Baumgartner HR. Collagen type III induced ex vivo thrombogenesis in humans: Role of platelets and leukocytes in deposition of fibrin. Arteriosclerosis 1990; 10: 276-284
    CrossrefPubMedGoogle Scholar
  • 26 Miller EF, Rhodes RK. Preparation and characterization of the different types of collagen. Methods Enzymol 1982; 82: 32-41
    PubMedGoogle Scholar
  • 27 Bruns RR, Gross J. High resolution analysis of the quarter stagger model of the collagen fibril. Biopolymers 1977; 13: 931-941
    PubMedGoogle Scholar
  • 28 Woessner JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this amino acid. Arch Biochem Biophys 1961; 93: 440-447
    CrossrefPubMedGoogle Scholar
  • 29 Muggli R, Baumgartner HR, Tschopp TB, Keller H. Automated microdensitometry and, protein assays as a measure for platelet adhesion and aggregation on collagen-coated slides under controlled flow conditions. J Lab Clin Med 1980; 95: 195-207
    PubMedGoogle Scholar
  • 30 Sakariassen KS, Kuhn H, Muggli R, Baumgartner HR. Growth and stability of thrombi in flowing blood: assessment of platelet-surface interactions with computer-assisted morphometry. Thromb Haemostas 1988; 60: 392-398
    PubMedGoogle Scholar
  • 31 Baumgartner HR, Muggli R. Adhesion and aggregation: morphological demonstration and quantitation in vivo and in vitro. In: Platelets in Biology and Pathology. Gordon JL. (ed) Elsevier/North Holland Biomedical, Amsterdam: 1976. pp 23-60
    Google Scholar
  • 32 Thorell L, Blombäck B. Purification of the factor VIII complex. Thromb Res 1984; 35: 431-450
    CrossrefPubMedGoogle Scholar
  • 33 Girma JP, Takahashi Y, Yoshioka A, Diaz J, Meyer D. Ristocetin and botrocetin involve two distinct domains of von Willebrand Factor for binding to platelet membrane glycoprotein lb. Thromb Haemostas 1990; 64: 326-332
    PubMedGoogle Scholar
  • 34 Takahashi Y, Kalafatis M, Girma JP, Sewerin K, Andersson LO, Meyer D. Localization of a factor VIII binding domain on a 34 kilodalton fragment of the N-terminal portion of von Willebrand Factor. Blood 1987; 70: 1679-1682
    PubMedGoogle Scholar
  • 35 Layet S, Girma JP, Obert B, Peynaud-Debayle E, Bihoreau N, Meyer D. Evidence that a secondary binding and protecting site for Factor VIII on von Willebrand Factor is highly unlikely. Biochem J 1992; 282: 129-137
    CrossrefPubMedGoogle Scholar
  • 36 Fine JM, Steinbuch M. A simple technique for the isolation of monoclonal IgG and IgA. Rev Eur Et Clin Biol 1970; 15: 1115-1121
    PubMedGoogle Scholar
  • 37 Fujimura Y, Titani K, Usami Y, Suzuki M, Oyama R, Matsui T, Fukui H, Sugimoto M, Ruggeri ZM. Isolation and chemical characterization of two structurally and functionally distinct forms of botrocetin, the platelet coagglutinin isolated from the venom of Bothrops Jararaca. Biochemistry 1991; 30: 1937-1964
    PubMedGoogle Scholar
  • 38 Pietu G, Fressinaud E, Girma JP, Nieuwenhuis HK, Rothschild C, Meyer D. Binding of von Willebrand factor to collagen and to collagen-stimulated platelets. J Lab Clin Med 1987; 109: 637-646
    PubMedGoogle Scholar
  • 39 Allain JP, Cooper HA, Wagner RH, Brinkhous KM. Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand Factor and platelet aggregating factor. J Lab Clin Med 1975; 85: 318-328
    PubMedGoogle Scholar
  • 40 Fraker PJ, Speck JC. Proteins and cell membrane iodinations with a sparingly soluble chloroamide, 1, 3, 4, 6-tetrachloro-3a, 6a diphenyl-glycoluril. Biochem Biophys Res Commun 1978; 80: 849-857
    CrossrefPubMedGoogle Scholar
  • 41 Fujimura Y, Titani K, Holland LZ, Roberts JR, Kostel P, Ruggeri ZM, Zimmermann TS. A heparin-binding domain of human von Willebrand Factor. Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728. J Biol Chem 1987; 262: 1734-1739
    PubMedGoogle Scholar
  • 42 Sakariassen KS, Nievelstein PFEM, Coller BS, Sixma JJ. The role of platelet membrane glycoproteins IIb and IIb-IIIa in platelet adherence to human artery subendothelium. Br J Haematol 1986; 63: 681-691
    CrossrefPubMedGoogle Scholar
  • 43 Fressinaud E, Baruch D, Girma JP, Sakariassen KS, Baumgartner HR, Meyer D. von Willebrand Factor-mediated adhesion to collagen involves platelet membrane glycoprotein IIb-IIIa as well as glycoprotein Ib. J Lab Clin Med 1988; 112: 58-67
    PubMedGoogle Scholar
  • 44 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggeri ZM. The role of von Willebrand Factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234-1240
    CrossrefPubMedGoogle Scholar
  • 45 Bisson C, Ceriani R, Bader R, Cremonesi P, Mannucci PM, Paggella PG, Pareti PI. Binding of certain dyes to vWF through different sites. Thromb Res 1991; suppl XIII 13 (Abstract)
    PubMedGoogle Scholar
  • 46 Sobel M, McNeill PM, Carlson PL, Kermode JC, Adelman B, Conroy R, Marques D. Heparin inhibition of von Willebrand Factor-dependent platelet function in vitro and in vivo. J Clin Invest 1991; 87: 1787-1793
    CrossrefPubMedGoogle Scholar