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Thromb Haemost 2008; 99(02): 264-270
DOI: 10.1160/TH07-10-0638
Theme Issue Article
Schattauer GmbH

Glycoprotein Ibα and von Willebrand factor in primary platelet adhesion and thrombus formation: Lessons from mutant mice

Wolfgang Bergmeier
1   Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
,
Anil K. Chauhan
2   Immune Disease Institute
3   Department of Pathology, Harvard Medical School, Boston, Massachussetts, USA
,
Denisa D. Wagner
2   Immune Disease Institute
3   Department of Pathology, Harvard Medical School, Boston, Massachussetts, USA
› Author Affiliations
Financial support: The work presented from our laboratories was supported by an American Heart Association Scientist Development Grant 0630044N (to W.B.), National Heart, Lung, and Blood Institute of the National Institutes of Health grants R37 HL41002 and P01 HL066105 (to D.D.W.), and by a Sponsored Research Agreement from Baxter, Vienna, Austria (to A.K.C. and D.D.W).
Further Information

Publication History

Received: 29 October 2007

Accepted after major revision: 11 January 2007

Publication Date:
24 November 2017 (online)

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Summary

The von Willebrand factor (VWF) receptor complex, glycoprotein (GP)Ib-V-IX, and its main ligand VWF play a key role in the adhesion process of platelets to sites of vascular injury. Recent studies in mutant mice have shed new light on the importance of either molecule for the development of arterial and venous thrombosis. In this review, we summarize the most important aspects from these studies.

Keywords

Thrombosis - glycoprotein - vonWillebrand factor - mutant - mice
 

  • References

  • 1 Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6: 217-246.
    CrossrefPubMedSearch in Google Scholar
  • 2 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424.
    CrossrefPubMedSearch in Google Scholar
  • 3 Bowie EJ, Solberg Jr. LA, Fass DN. et al. Transplantation of normal bone marrow into a pig with severe von Willebrand's disease. J Clin Invest 1986; 78: 26-30.
    CrossrefPubMedSearch in Google Scholar
  • 4 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-190.
    CrossrefPubMedSearch in Google Scholar
  • 5 Arya M, Anvari B, Romo GM. et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood 2002; 99: 3971-3977.
    CrossrefPubMedSearch in Google Scholar
  • 6 Sporn LA, Marder VJ, Wagner DD. von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. Blood 1987; 69: 1531-1534.
    PubMedSearch in Google Scholar
  • 7 Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood 1994; 83: 2171-2179.
    PubMedSearch in Google Scholar
  • 8 Furlan M, Robles R, Lamie B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 1996; 87: 4223-4234.
    PubMedSearch in Google Scholar
  • 9 Motto DG, Chauhan AK, Zhu G. et al. Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest 2005; 115: 2752-2761.
    CrossrefPubMedSearch in Google Scholar
  • 10 Banno F, Kokame K, Okuda T. et al. Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. Blood 2006; 107: 3161-3166.
    CrossrefPubMedSearch in Google Scholar
  • 11 Veyradier A, Lavergne JM, Ribba AS. et al. Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). J Thromb Haemost 2004; 2: 424-429.
    CrossrefPubMedSearch in Google Scholar
  • 12 Furlan M, Lammle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol 2001; 14: 437-454.
    CrossrefPubMedSearch in Google Scholar
  • 13 Weiss HJ, Sussman II, Hoyer LW. Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease. J Clin Invest 1977; 60: 390-404.
    CrossrefPubMedSearch in Google Scholar
  • 14 Denis C, Methia N, Frenette PS. et al. A mouse model of severe von Willebrand disease: defects in haemostasis and thrombosis. Proc Natl Acad Sci USA 1998; 95: 9524-9529.
    CrossrefPubMedSearch in Google Scholar
  • 15 Bernard J, Soulier JP. Sur une nouvelle variete de dystrophie thrombocytaire-haemorragipare congenitale. Semin Hop Paris 1948; 24: 3217.
    PubMedSearch in Google Scholar
  • 16 Caen JP, Nurden AT, Jeanneau C. et al. Bernard-Soulier syndrome: a new platelet glycoprotein abnormality. Its relationship with platelet adhesion to subendothelium and with the factor VIII von Willebrand protein. J Lab Clin Med 1976; 87: 586-596.
    PubMedSearch in Google Scholar
  • 17 Ware J, Russell S, Ruggeri ZM. Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier syndrome. Proc Natl Acad Sci USA 2000; 97: 2803-2808.
    CrossrefPubMedSearch in Google Scholar
  • 18 Lopez JA, Chung DW, Fujikawa K. et al. The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence. Proc Natl Acad Sci USA 1988; 85: 2135-2139.
    CrossrefPubMedSearch in Google Scholar
  • 19 Lopez JA, Chung DW, Fujikawa K. et al. Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein. Proc Natl Acad Sci USA 1987; 84: 5615-5619.
    CrossrefPubMedSearch in Google Scholar
  • 20 Lanza F, Morales M, de La Salle C. et al. Cloning and characterization of the gene encoding the human platelet glycoprotein V. A member of the leucine-rich glycoprotein family cleaved during thrombin-induced platelet activation. J Biol Chem 1993; 268: 20801-20807.
    PubMedSearch in Google Scholar
  • 21 Bergmeier W, Rackebrandt K, Schroder W. et al. Structural and functional characterization of the mouse von Willebrand factor receptor GPIb-IX with novel monoclonal antibodies. Blood 2000; 95: 886-893.
    PubMedSearch in Google Scholar
  • 22 Takamatsu J, Horne 3rd MK, Gralnick HR. Identification of the thrombin receptor on human platelets by chemical crosslinking. J Clin Invest 1986; 77: 362-368.
    CrossrefPubMedSearch in Google Scholar
  • 23 Yamamoto N, Greco NJ, Barnard MR. et al. Glycoprotein Ib (GPIb)-dependent and GPIb-independent pathways of thrombin-induced platelet activation. Blood 1991; 77: 1740-1748.
    PubMedSearch in Google Scholar
  • 24 Bradford HN, Dela Cadena RA, Kunapuli SP. et al. Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex. Blood 1997; 90: 1508-1515.
    PubMedSearch in Google Scholar
  • 25 Bradford HN, Pixley RA, Colman RW. Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem 2000; 275: 22756-22763.
    CrossrefPubMedSearch in Google Scholar
  • 26 Baglia FA, Badellino KO, Li CQ. et al. Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin. J Biol Chem 2002; 277: 1662-1668.
    CrossrefPubMedSearch in Google Scholar
  • 27 Jurk K, Clemetson KJ, de Groot PG. et al. Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor. Faseb J 2003; 17: 1490-1492.
    CrossrefPubMedSearch in Google Scholar
  • 28 Simon DI, Chen Z, Xu H. et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
    CrossrefPubMedSearch in Google Scholar
  • 29 Wang Y, Sakuma M, Chen Z. et al. Leukocyte engagement of platelet glycoprotein Ibalpha via the integrin Mac-1 is critical for the biological response to vascular injury. Circulation 2005; 112: 2993-3000.
    PubMedSearch in Google Scholar
  • 30 Romo GM, Dong JF, Schade AJ. et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999; 190: 803-814.
    CrossrefPubMedSearch in Google Scholar
  • 31 Andrews RK, Shen Y, Gardiner EE. et al. The glycoprotein Ib-IX-V complex in platelet adhesion and signaling. Thromb Haemost 1999; 82: 357-364.
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Ozaki Y, Asazuma N, Suzuki-Inoue K. et al. Platelet GPIb-IX-V-dependent signaling. J Thromb Haemost 2005; 3: 1745-1751.
    CrossrefPubMedSearch in Google Scholar
  • 33 Sakariassen KS, Fressinaud E, Girma JP. et al. Role of platelet membrane glycoproteins and von Willebrand factor in adhesion of platelets to subendothelium and collagen. Ann NY Acad Sci 1987; 516: 52-65.
    CrossrefPubMedSearch in Google Scholar
  • 34 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-Von Willebrand factor bound to the subendothelium. Nature 1979; 279: 636-638.
    CrossrefPubMedSearch in Google Scholar
  • 35 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84: 289-297.
    CrossrefPubMedSearch in Google Scholar
  • 36 Goto S, Ikeda Y, Saldivar E. et al. Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest 1998; 101: 479-486.
    CrossrefPubMedSearch in Google Scholar
  • 37 Kulkarni S, Dopheide SM, Yap CL. et al. A revised model of platelet aggregation. J Clin Invest 2000; 105: 783-791.
    CrossrefPubMedSearch in Google Scholar
  • 38 Reininger AJ, Heijnen HF, Schumann H. et al. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood 2006; 107: 3537-3545.
    CrossrefPubMedSearch in Google Scholar
  • 39 Ruggeri ZM, Orje JN, Habermann R. et al. Activation-independent platelet adhesion and aggregation under elevated shear stress. Blood 2006; 108: 1903-1910.
    CrossrefPubMedSearch in Google Scholar
  • 40 Siegel JM, Markou CP, Ku DN. et al. A scaling law for wall shear rate through an arterial stenosis. J Biomech Eng 1994; 116: 446-451.
    CrossrefPubMedSearch in Google Scholar
  • 41 Strony J, Beaudoin A, Brands D. et al. Analysis of shear stress and haemodynamic factors in a model of coronary artery stenosis and thrombosis. Am J Physiol 1993; 265: H1787-1796.
    PubMedSearch in Google Scholar
  • 42 Vanhoorelbeke K, Ulrichts H, Van de, Walle G. et al. Inhibition of platelet glycoprotein Ib and its antithrombotic potential. Curr Pharm Des 2007; 13: 2684-2697.
    CrossrefPubMedSearch in Google Scholar
  • 43 De Meyer SF, Vanhoorelbeke K, Ulrichts H. et al. Development of monoclonal antibodies that inhibit platelet adhesion or aggregation as potential antithrombotic drugs. Cardiovasc Hematol Disord Drug Targets 2006; 6: 191-207.
    CrossrefPubMedSearch in Google Scholar
  • 44 Bonnefoy A, Vermylen J, Hoylaerts MF. Inhibition of von Willebrand factor-GPIb/IX/V interactions as a strategy to prevent arterial thrombosis. Expert Rev Cardiovasc Ther 2003; 1: 257-269.
    CrossrefPubMedSearch in Google Scholar
  • 45 Ni H, Denis CV, Subbarao S. et al. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest 2000; 106: 385-392.
    CrossrefPubMedSearch in Google Scholar
  • 46 Sawada Y, Fass DN, Katzmann JA. et al. Haemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor. Blood 1986; 67: 1229-1239.
    PubMedSearch in Google Scholar
  • 47 Dubois C, Panicot-Dubois L, Gainor JF. et al. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model. J Clin Invest 2007; 117: 953-960.
    CrossrefPubMedSearch in Google Scholar
  • 48 Ni H, Yuen PS, Papalia JM. et al. Plasma fibronectin promotes thrombus growth and stability in injured arterioles. Proc Natl Acad Sci USA 2003; 100: 2415-2419.
    CrossrefPubMedSearch in Google Scholar
  • 49 Matuskova J, Chauhan AK, Cambien B. et al. Decreased Plasma Fibronectin Leads to Delayed Thrombus Growth in Injured Arterioles. Arterioscler Thromb Vasc Biol 2006; 26: 1391-1396.
    CrossrefPubMedSearch in Google Scholar
  • 50 Denis CV, Wagner DD. Platelet adhesion receptors and their ligands in mouse models of thrombosis. Arterioscler Thromb Vasc Biol 2007; 27: 728-739.
    CrossrefPubMedSearch in Google Scholar
  • 51 Kanaji T, Russell S, Ware J. Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome. Blood 2002; 100: 2102-2107.
    CrossrefPubMedSearch in Google Scholar
  • 52 Bergmeier W, Piffath CL, Goerge T. et al. The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci USA 2006; 103: 16900-16905.
    CrossrefPubMedSearch in Google Scholar
  • 53 Bonnefoy A, Daenens K, Feys HB. et al. Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS-13. Blood 2006; 107: 955-964.
    CrossrefPubMedSearch in Google Scholar
  • 54 Konstantinides S, Ware J, Marchese P. et al. Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost 2006; 4: 2014-2021.
    CrossrefPubMedSearch in Google Scholar
  • 55 Jain S, Zuka M, Liu J. et al. Platelet glycoprotein Ib alpha supports experimental lung metastasis. Proc Natl Acad Sci USA 2007; 104: 9024-9028.
    CrossrefPubMedSearch in Google Scholar
  • 56 Strassel C, Nonne C, Eckly A. et al. Decreased thrombotic tendency in mouse models of the Bernard-Soulier syndrome. Arterioscler Thromb Vasc Biol 2007; 27: 241-247.
    CrossrefPubMedSearch in Google Scholar
  • 57 Mannucci PM. Platelet von Willebrand factor in inherited and acquired bleeding disorders. Proc Natl Acad Sci USA 1995; 92: 2428-2432.
    CrossrefPubMedSearch in Google Scholar
  • 58 Mazzucato M, Spessotto P, Masotti A. et al. Identification of domains responsible for von Willebrand factor type VI collagen interaction mediating platelet adhesion under high flow. J Biol Chem 1999; 274: 3033-3041.
    CrossrefPubMedSearch in Google Scholar
  • 59 Badimon L, Badimon JJ, Turitto VT. et al. Role of von Willebrand factor in mediating platelet-vessel wall interaction at low shear rate; the importance of perfusion conditions. Blood 1989; 73: 961-967.
    PubMedSearch in Google Scholar
  • 60 Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998; 94: 657-666.
    CrossrefPubMedSearch in Google Scholar
  • 61 Houdijk WP, Sakariassen KS, Nievelstein PF. et al. Role of factor VIII-von Willebrand factor and fibronectin in the interaction of platelets in flowing blood with monomeric and fibrillar human collagen types I and III. J Clin Invest 1985; 75: 531-540.
    CrossrefPubMedSearch in Google Scholar
  • 62 Stel HV, Sakariassen KS, de Groot PG. et al. Von Willebrand factor in the vessel wall mediates platelet adherence. Blood 1985; 65: 85-90.
    PubMedSearch in Google Scholar
  • 63 Oury C, Daenens K, Hu H. et al. ERK2 activation in arteriolar and venular murine thrombosis: platelet receptor GPIb vs. P2X. J Thromb Haemost 2006; 4: 443-452.
    CrossrefPubMedSearch in Google Scholar
  • 64 Yeh CH, Chang MC, Peng HC. et al. Pharmacological characterization and antithrombotic effect of agkistin, a platelet glycoprotein Ib antagonist. Br J Pharmacol 2001; 132: 843-850.
    CrossrefPubMedSearch in Google Scholar
  • 65 Chang MC, Lin HK, Peng HC. et al. Antithrombotic effect of crotalin, a platelet membrane glycoprotein Ib antagonist from venom of Crotalus atrox. Blood 1998; 91: 1582-1589.
    PubMedSearch in Google Scholar
  • 66 Yamamoto H, Vreys I, Stassen JM. et al. Antagonism of vWF inhibits both injury induced arterial and venous thrombosis in the hamster. Thromb Haemost 1998; 79: 202-210.
    Thieme ConnectPubMedSearch in Google Scholar
  • 67 Bernat A, Lale A, Herbert JM. Aurin tricarboxylic acid inhibits experimental venous thrombosis. Thromb Res 1994; 74: 617-627.
    CrossrefPubMedSearch in Google Scholar
  • 68 Chauhan AK, Kisucka J, Lamb CB. et al. von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood 2007; 109: 2424-2429.
    CrossrefPubMedSearch in Google Scholar
  • 69 Myers Jr. D, Farris D, Hawley A. et al. Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis. J Surg Res 2002; 108: 212-221.
    CrossrefPubMedSearch in Google Scholar
  • 70 Moake JL. von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura. Semin Hematol 2004; 41: 4-14.
    CrossrefPubMedSearch in Google Scholar
  • 71 Dong JF, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039.
    CrossrefPubMedSearch in Google Scholar
  • 72 Chauhan AK, Motto DG, Lamb CB. et al. Systemic antithrombotic effects of ADAMTS13. J Exp Med 2006; 203: 767-776.
    CrossrefPubMedSearch in Google Scholar
  • 73 Donadelli R, Orje JN, Capoferri C. et al. Size regulation of von Willebrand factor-mediated platelet thrombi by ADAMTS13 in flowing blood. Blood 2006; 107: 1943-1950.
    CrossrefPubMedSearch in Google Scholar
  • 74 Hennan JK, Swillo RE, Morgan GA. et al. Pharmacologic inhibition of platelet vWF-GPIb alpha interaction prevents coronary artery thrombosis. Thromb Haemost 2006; 95: 469-475.
    Thieme ConnectPubMedSearch in Google Scholar