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Thromb Haemost 2002; 88(06): 1039-1046
DOI: 10.1055/s-0037-1613352
Involvement of Thrombin Receptors in the Subject-dependent Variability in Ca2+ Signal Generation
Schattauer GmbH

Pathogenic Effects of Anti-Glycoprotein Ib Antibodies on Megakaryocytes and Platelets

Gulie Alimardani
1   Département d’hématologie, INSERM U.567, Institut Cochin, Paris
2   Laboratoire d’hématologie, CHU Amiens, Amiens
,
Josette Guichard
1   Département d’hématologie, INSERM U.567, Institut Cochin, Paris
,
Serge Fichelson
1   Département d’hématologie, INSERM U.567, Institut Cochin, Paris
,
Elisabeth M. Cramer
1   Département d’hématologie, INSERM U.567, Institut Cochin, Paris
3   Service d’hématologie et d’immunologie, Hôpital Ambroise Paré (AP-HP) and Faculté Paris-Ile de France-Ouest
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Further Information

Publication History

Received 30 June 2002

Accepted 03 September 2002

Publication Date:
09 December 2017 (online)

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Summary

Antibodies directed against the glycoprotein (GP) Ib have been identified as the potential cause of various platelet disorders: Immune thrombocytopenic purpura (ITP) may be caused by such autoantibodies; Anti-thrombotic drugs targeting GPIb also induce thrombocytopenia. In order to elucidate the potential mechanism(s) of the anti-GPIb effects, we have examined by electron microscopy (EM) the effect of several antibodies directed against GPIb and GPIIb-IIIa on human culture megakaryocytes (MK). Virtually all antibodies to GPIb enhanced the interaction of newly formed platelets with MK when compared to other antibodies. These effects were retrieved when antibodies were tested on platelets. We conclude that antibodies to GPIb can potentially inhibit platelet release by MK, and can also induce homotypic platelet adhesion. These results may have implications in the pathophysiology of thrombocytopenia and platelet recovery in ITP, and shed light on the pathological effect of anti-GPIb antibodies used as antithrombotic drugs.

Keywords

Megakaryocytes - platelets - GPIb
 

  • References

  • 1 Andrews RK, Lopez JA, Berndt MC. Molecular mechanisms of platelet adhesion and activation. Int J Biochem Cell Biol 1997; 29: 91-105.
    CrossrefPubMedGoogle Scholar
  • 2 Lopez JA. The platelet glycoprotein Ib-IX complex. Blood Coagul Fibrinolysis 1994; 05: 97-119.
    CrossrefPubMedGoogle Scholar
  • 3 Lopez JA, Dong JF. Structure and function of the glycoprotein Ib-IX-V complex. Curr Opin Hematol 1997; 04: 323-9.
    CrossrefPubMedGoogle Scholar
  • 4 Debili N, Kieffer N, Nakazawa M, Guichard J, Titeux M, Cramer E, Breton-Gorius J, Vainchenker W. Expression of platelet glycoprotein Ib by cultured human megakaryocytes: ultrastructural localization and biosynthesis. Blood 1990; 76: 368-76.
    PubMedGoogle Scholar
  • 5 Simon DI, Chen Z, Xu H, Li CQ, Dong J, McIntire LV, Ballantyne CM, Zhang L, Furman MI, Berndt MC, Lopez JA. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
    CrossrefPubMedGoogle Scholar
  • 6 Cauwenberghs N, Meiring M, Vauterin S, van Wyk V, Lamprecht S, Roodt JP, Novak L, Harsfalvi J, Deckmyn H, Kotze HF. Antithrombotic effect of platelet glycoprotein Ib-blocking monoclonal antibody Fab fragments in nonhuman primates. Arterioscler Thromb Vasc Biol 2000; 20: 1347-53.
    CrossrefPubMedGoogle Scholar
  • 7 Cadroy Y, Hanson SR, Kelly AB, Marzec UM, Evatt BL, Kunicki TJ, Montgomery RR, Harker LA. Relative antithrombotic effects of monoclonal antibodies targeting different platelet glycoprotein-adhesive molecule interactions in nonhuman primates. Blood 1994; 83: 3218-24.
    PubMedGoogle Scholar
  • 8 Kiefel V, Santoso S, Kaufmann E, Mueller-Eckhardt C. Autoantibodies against platelet glycoprotein Ib/IX: a frequent finding in autoimmune thrombocytopenic purpura. Br J Haematol 1991; 79: 256-62.
    CrossrefPubMedGoogle Scholar
  • 9 McMillan R, Tani P, Millard F, Berchtold P, Renshaw L, Woods Jr VL. Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP. Blood 1987; 70: 1040-5.
    PubMedGoogle Scholar
  • 10 Szatkowski NS, Kunicki TJ, Aster RH. Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura. Blood 1986; 67: 310-5.
    PubMedGoogle Scholar
  • 11 Woods Jr. VL, Kurata Y, Montgomery RR, Tani P, Mason D, Oh EH, McMillan R. Autoantibodies against platelet glycoprotein Ib in patients with chronic immune thrombocytopenic purpura. Blood 1984; 64: 156-60.
    PubMedGoogle Scholar
  • 12 McMillan R. The pathogenesis of chronic immune (idiopathic) thrombocytopenic purpura. Semin Hematol 2000; 37: 5-9.
    PubMedGoogle Scholar
  • 13 Berchtold P, Wenger M. Autoantibodies against platelet glycoproteins in autoimmune thrombocytopenic purpura: their clinical significance and response to treatment. Blood 1993; 81: 1246-50.
    PubMedGoogle Scholar
  • 14 Suvajdzic N, Rolovic Z, Elezovic I, Colovic M. Megakaryocytopoiesis in refractory chronic immune thrombocytopenia. Hematol Cell Ther 1999; 41: 163-8.
    CrossrefPubMedGoogle Scholar
  • 15 Wang ZY, Shen ZX. Megakaryocytes and platelets in immune thrombocytopenic purpura. Baillieres Clin Haematol 1997; 10: 89-107.
    CrossrefPubMedGoogle Scholar
  • 16 He R, Reid DM, Jones CE, Shulman NR. Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura. Blood 1994; 83: 1024-32.
    PubMedGoogle Scholar
  • 17 Beardsley DS, Ertem M. Platelet autoantibodies in immune thrombocytopenic purpura. Transfus Sci 1998; 19: 237-44.
    CrossrefPubMedGoogle Scholar
  • 18 Berchtold P, Muller D, Beardsley D, Fujisawa K, Kaplan C, Kekomaki R, Lipp E, Morell-Kopp MC, Kiefel V, McMillan R, von dem Borne AE, Imbach P. International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies. Br J Haematol 1997; 96: 477-83.
    CrossrefPubMedGoogle Scholar
  • 19 Chong BH, Keng TB. Advances in the diagnosis of idiopathic thrombocytopenic purpura. Semin Hematol 2000; 37: 249-60.
    CrossrefPubMedGoogle Scholar
  • 20 Warner MN, Moore JC, Warkentin TE, Santos AV, Kelton JG. A prospective study of protein-specific assays used to investigate idiopathic thrombocytopenic purpura. Br J Haematol 1999; 104: 442-7.
    CrossrefPubMedGoogle Scholar
  • 21 Hou M, Stockelberg D, Kutti J, Wadenvik H. Antibodies against platelet GPIb/IX, GPIIb/IIIa, and other platelet antigens in chronic idiopathic thrombocytopenic purpura. Eur J Haematol 1995; 55: 307-14.
    PubMedGoogle Scholar
  • 22 Nomura S, Yanabu M, Soga T, Kido H, Fukuroi T, Yamaguchi K, Nagata H, Kokawa T, Yasunaga K. Analysis of idiopathic thrombocytopenic purpura patients with antiglycoprotein IIb/IIIa or Ib autoantibodies. Acta Haematol 1991; 86: 25-30.
    CrossrefPubMedGoogle Scholar
  • 23 McMillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura. Semin Hematol 2000; 37: 239-48.
    CrossrefPubMedGoogle Scholar
  • 24 Mehta YS, Pathare AV, Badakere SS, Ghosh K, Mohanty D. Influence of auto-antibody specificities on the clinical course in patients with chronic and acute ITP. Platelets 2000; 11: 94-8.
    CrossrefPubMedGoogle Scholar
  • 25 Hagberg IA, Lyberg T. Blood platelet activation evaluated by flow cytometry: optimised methods for clinical studies. Platelets 2000; 11: 137-50.
    CrossrefPubMedGoogle Scholar
  • 26 Cramer EM, Caen JP, Drouet L, Breton-Gorius J. Absence of tubular structures and immunolabeling for von Willebrand factor in the platelet alpha-granules from porcine von Willebrand disease. Blood 1986; 68: 774-8.
    PubMedGoogle Scholar
  • 27 Cramer EM, Meyer D, le Menn R, Breton-Gorius J. Eccentric localization of von Willebrand factor in an internal structure of platelet alpha-granule resembling that of Weibel-Palade bodies. Blood 1985; 66: 710-3.
    CrossrefPubMedGoogle Scholar
  • 28 Cramer EM, Norol F, Guichard J, Breton-Gorius J, Vainchenker W, Masse JM, Debili N. Ultrastructure of platelet formation by human megakaryocytes cultured with the Mpl ligand. Blood 1997; 89: 2336-46.
    PubMedGoogle Scholar
  • 29 Vitrat N, Cohen-Solal K, Norol F, Guichard J, Cramer E, Vainchenker W, Wendling F, Debili N. Compared effects of Mpl ligand and other cytokines on human MK differentiation. Stem Cells 1998; 02: 37-51.
    PubMedGoogle Scholar
  • 30 Takahashi R, Sekine N, Nakatake T. Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Blood 1999; 93: 1951-8.
    CrossrefPubMedGoogle Scholar
  • 31 Berndt MC, Du XP, Booth WJ. Ristocetin-dependent reconstitution of binding of von Willebrand factor to purified human platelet membrane glycoprotein Ib-IX complex. Biochemistry 1988; 27: 633-40.
    CrossrefPubMedGoogle Scholar
  • 32 Williamson D, Giuliano S, Jackson SP. Platelet adhesion receptors: novel targets for anti-thrombotic therapy. Aust N Z J Med 1999; 29: 452-61.
    CrossrefPubMedGoogle Scholar
  • 33 Schafer AI. Antiplatelet therapy. Am J Med 1996; 101: 199-209.
    CrossrefPubMedGoogle Scholar
  • 34 Coller BS, Anderson K, Weisman HF. New antiplatelet agents: platelet GPIIb/IIIa antagonists. Thromb Haemost 1995; 74: 302-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Neumann FJ, Kastrati A, Schmitt C, Blasini R, Hadamitzky M, Mehilli J, Gawaz M, Schleef M, Seyfarth M, Dirschinger J, Schomig A. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction. J Am Coll Cardiol 2000; 35: 915-21.
    CrossrefPubMedGoogle Scholar
  • 36 Hayes R, Chesebro JH, Fuster V, Dangas G, Fallon JT, Sharma SK, Coller BS, Badimon L, Marmur JD, Badimon JJ. Antithrombotic effects of abciximab. Am J Cardiol 2000; 85: 1167-72.
    CrossrefPubMedGoogle Scholar
  • 37 Chang MC, Lin HK, Peng HC, Huang TF. Antithrombotic effect of crotalin, a platelet membrane glycoprotein Ib antagonist from venom of Crotalus atrox. Blood 1998; 91: 1582-9.
    PubMedGoogle Scholar
  • 38 Yeh CH, Chang MC, Peng HC, Huang TF. Pharmacological characterization and antithrombotic effect of agkistin, a platelet glycoprotein Ib antagonist. Br J Pharmacol 2001; 132: 843-50.
    CrossrefPubMedGoogle Scholar