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Thromb Haemost 1999; 81(02): 281-285
DOI: 10.1055/s-0037-1614458
Review Articles
Schattauer GmbH

Modulation of Platelet-neutrophil Interaction with Pharmacological Inhibition of Fibrinogen Binding to Platelet GPIIb/IIIa Receptor

Zihui Xiao
1   From the Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada
,
Pierre Théroux
2   The Department of Medicine, University of Montreal, Montreal, Quebec, Canada
,
Mony Frojmovic
3   Department of Physiology, McGill University, Montreal, Quebec, Canada
› Author Affiliations
Further Information

Publication History

Received03 June 1998

Accepted after revision04 November 1998

Publication Date:
08 December 2017 (online)

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Summary

The study investigated how drug inhibition of the GPIIb/IIIa receptor influences the interactions between platelets and leukocytes. These interactions are believed to play an important role in the etiology of the acute coronary syndromes. Thirty patients with unstable angina or non-Q-wave myocardial infarction were studied before the administration of tirofiban or placebo and after 4 h and 72 h. Platelet-leukocyte aggregates were characterized in whole blood using three-colour flow cytometry. The leukocyte population was isolated by a nucleic acid probe (LDS 751) and platelet-neutrophil coaggregates identified as particles binding both anti-CD42a-FITC and anti-CD45-PE. Tirofiban decreased by 25% the density of platelets in circulating platelet-neutrophil coaggregates (p <0.01), and prevented the increase induced by platelet agonist stimulation (p <0.0001). The reduction correlated with inhibition of fibrinogen binding to platelet (p <0.0001) and with inhibition of platelet aggregation (p <0.0001). The percentage of neutrophils with bound platelets following platelet agonist stimulation was, however, increased following GPIIb/IIIa inhibition. Thus, inhibition of GPIIb/IIIa receptor promotes platelet-neutrophil adhesion, but markedly reduces the binding density of platelets in the coaggregates.

 

  • References

  • 1 Coller BS. Blockade of platelet GPIIb/IIIa receptors as an antithrombotic strategy. Circulation 1995; 92: 2373-80.
    CrossrefPubMedGoogle Scholar
  • 2 Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995; 332: 1553-9.
    CrossrefPubMedGoogle Scholar
  • 3 The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: 956-61.
    CrossrefPubMedGoogle Scholar
  • 4 The PRISM-PLUS Investigators. Inhibition of platelet receptor glycoprotein IIb/IIIa with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998; 338: 1488-97.
    CrossrefPubMedGoogle Scholar
  • 5 Tschoepe D. Adhesion molecules influencing atherosclerosis. Diabetes Res Clin Pract 1996; 30 suppl 19-24.
    CrossrefPubMedGoogle Scholar
  • 6 Neri Serneri GG, Prisco D, Martini F, Gori AM, Brunelli T, Poggesi L, Rostagno C, Gensini GF, Abbate R. Acute T-cell activation is detectable in unstable angina. Circulation 1997; 95: 1806-12.
    CrossrefPubMedGoogle Scholar
  • 7 Kirchhofer D, Riederer MA, Baumgartner HR. Specific accumulation of circulating monocytes and polymorphonuclear leukocytes on platelet thrombi in a vascular injury model. Blood 1997; 89: 1270-8.
    PubMedGoogle Scholar
  • 8 Ott I, Neumann FJ, Gawaz M, Schmitt M, Schomig A. Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation 1996; 94: 1239-46.
    CrossrefPubMedGoogle Scholar
  • 9 Mickelson JK, Lakkis NM, Villarreal-Levy G, Hughes BJ, Smith CW. Leukocyte activation with platelet adhesion after coronary angioplasty: A mechanism for recurrent disease?. J Am Coll Cardiol 1996; 28: 345-53.
    CrossrefPubMedGoogle Scholar
  • 10 Katopodis JN, Kolodny L, Jy W, Horstman LL, De Marchena EJ, Tao JG, Haynes DH, Ahn YS. Platelet microparticles and calcium homeostasis in acute coronary ischemias. Am J Hematol 1997; 54: 95-101.
    CrossrefPubMedGoogle Scholar
  • 11 Buttrum SM, Hatton R, Nash GB. Selectin-mediated rolling of neutrophils on immobilized platelets. Blood 1993; 82: 1165-74.
    PubMedGoogle Scholar
  • 12 McEver RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest 1997; 100 suppl 97-103.
    PubMedGoogle Scholar
  • 13 Furie B, Furie BC. Leukocyte crosstalk at the vascular wall. Thromb Haemost 1997; 78: 306-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 1992; 359: 848-51.
    CrossrefPubMedGoogle Scholar
  • 15 Ruf A, Patscheke H. Platelet-induced neutrophil activation: platelet-expressed fibrinogen induces the oxidative burst in neutrophils by an interaction with CD11c/CD18. Br J Haematol 1995; 90: 791-6.
    CrossrefPubMedGoogle Scholar
  • 16 Diamond MS, Springer TA. A subpopulation of Mac-1 (CD11b/CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen. J Cell Biol 1993; 120: 545-56.
    CrossrefPubMedGoogle Scholar
  • 17 Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. Blood 1996; 88: 146-57.
    PubMedGoogle Scholar
  • 18 Evangelista V, Manarini S, Rotondo S, Martelli N, Polischuk R, McGregor JL, de Gaetano G, Cerletti C. Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the beta 2 integrin CD11b/CD18. Blood 1996; 88: 4183-94.
    PubMedGoogle Scholar
  • 19 Ostrovsky L, King AJ, Bond S, Mitchell D, Lorant DE, Zimmerman GA, Larsen R, Niu XF, Kubes P. A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process. Blood 1998; 91: 3028-36.
    PubMedGoogle Scholar
  • 20 Xiao ZH, Théroux P. Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation 1998; 97: 251-6.
    CrossrefPubMedGoogle Scholar
  • 21 Terstappen LW, Meiners H, Loken MR. A rapid sample preparation technique for flow cytometric analysis of immunofluorescence allowing absolute enumeration of cell subpopulations. J Immunol Methods 1989; 123: 103-12.
    CrossrefPubMedGoogle Scholar
  • 22 Simon I S, Rochon YP, Lynam EB, Smith CW, Anderson DC, Sklar LA. Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation. Blood 1993; 82: 1097-106.
    PubMedGoogle Scholar
  • 23 Xia Z, Wong T, Liu Q, Kasirer-Friede A, Brown E, Frojmovic MM. Optimally functional fluorescein isothiocyanate-labelled fibrinogen for quantitative studies of binding to activated platelets and platelet aggregation. Br J Haematol 1996; 93: 204-14.
    CrossrefPubMedGoogle Scholar
  • 24 Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood 1987; 70: 307-15.
    PubMedGoogle Scholar
  • 25 Rinder HM, Bonan JL, Rinder CS, Ault KA, Smith BR. Dynamics of leukocyte-platelet adhesion in whole blood. Blood 1991; 78: 1730-7.
    PubMedGoogle Scholar
  • 26 Rinder HM, Bonan JL, Rinder CS, Ault KA, Smith BR. Activated and unactivated platelet adhesion to monocytes and neutrophils. Blood 1991; 78: 1760-9.
    PubMedGoogle Scholar
  • 27 Neri Serneri GG, Abbate R, Gori AM, Attanasio M, Martini F, Giusti B, Dabizzi P, Poggesi L, Modesti PA, Trotta F, Rostagno C, Boddi M, Gensini GF. A transient intermittent lymphocyte activation is responsible for the instability of angina. Circulation 1992; 86: 790-7.
    CrossrefPubMedGoogle Scholar
  • 28 Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation 1985; 71: 699-708.
    CrossrefPubMedGoogle Scholar
  • 29 Théroux P, Fuster V. Acute coronary syndromes. Unstable angina and non-Q-wave myocardial infarction. Circulation 1998; 97: 1195-206.
    CrossrefPubMedGoogle Scholar
  • 30 Davies MJ, Thomas AC, Knapman PA, Hangartner JR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986; 73: 418-27.
    CrossrefPubMedGoogle Scholar
  • 31 Entman ML, Ballantyne CM. Association of neutrophils with platelet aggregates in unstable angina. Should we alter therapy?. Circulation 1996; 94: 1206-8.
    CrossrefPubMedGoogle Scholar
  • 32 Akbar GK, Mills DC, Kunapuli SP. Characterization of extracellular nucleotide-induced Mac-1 surface expression on peripheral blood leukocytes. Biochem Biophys Res Commun 1997; 233: 71-5.
    CrossrefPubMedGoogle Scholar
  • 33 Gerszten RE, Chen J, Ishii M, Ishii K, Wang L, Nanevicz T, Turck CW, Vu TK, Coughlin SR. Specificity of the thrombin receptor for agonist peptide is defined by its extracellular surface. Nature 1994; 368: 648-51.
    CrossrefPubMedGoogle Scholar
  • 34 Anderson DC, Miller LJ, Schmalstieg FC, Rothlein R, Springer TA. Contributions of the Mac-1 glycoprotein family to adherence-dependent granulocyte functions: structure-function assessments employing subunit-specific monoclonal antibodies. J Immunol 1986; 137: 15-27.
    PubMedGoogle Scholar
  • 35 Wright SD, Weitz I J, Huang AJ, Levin SM, Silverstein SC, Loike JD. Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci USA 1988; 85: 7734-8.
    CrossrefPubMedGoogle Scholar
  • 36 Liu Q, Rooney MM, Kasirer-Friede A, Brown E, Lord ST, Frojmovic MM. Role of gamma chain Ala-Gly-Asp-Val and an alpha chain Arg-Gly-Asp-Ser sites of fibrinogen in coaggregation of platelets and fibrinogen-coated beads. Biochim Biophys Acta. 1998 In press
    PubMedGoogle Scholar
  • 37 Weber C, Springer TA. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. J Clin Invest 1997; 100: 2085-93.
    CrossrefPubMedGoogle Scholar
  • 38 Bazzoni G, Beltran Nunez A, Mascellani G, Bianchini P, Dejana E, Del Maschio A. Effect of heparin, dermatan sulfate, and related oligo-derivatives on human polymorphonuclear leukocyte functions. J Lab Clin Med 1993; 121: 268-75.
    PubMedGoogle Scholar
  • 39 Ferrer-Lopez P, Renesto P, Prevost MC, Gounon P, Chignard M. Heparin inhibits neutrophil-induced platelet activation via cathepsin G. J Lab Clin Med 1992; 119: 231-9.
    PubMedGoogle Scholar