Skip to main content
SpringerLink
Log in

Role of Glycoprotein IIb-IIIa (αIIbβ3-integrin) in Stimulation of Secretion from Platelet Granules

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

The involvement of glycoprotein (GP) IIb-IIIa (αIIbβ3-integrin) in the stimulation of secretion from platelet dense and α-granules was investigated. Fibrinogen binding with GP IIb-IIIa and platelet aggregation were inhibited by fragments of anti-GP IIb-IIIa monoclonal antibodies (monAB)—Fab fragment of antibody c7E3 (preparation ReoPro) and F(ab")2 fragment of antibody FraMon (preparation FRAMON). Suppression of GP IIb-IIIa receptor activity by both preparations led to 100% inhibition of [14C]serotonin secretion from dense granules upon platelet activation with ADP, to partial inhibition upon activation with thromboxane A2 analog U46619 (by 60-70%) and thrombin at 0.1 U/ml (by 40-50%), but did not decrease serotonin secretion induced by thrombin at 1 U/ml. ReoPro and FRAMON completely inhibited ADP-induced release of soluble P-selectin from platelet α-granules, but did not influence P-selectin secretion stimulated by U46619 and by both thrombin concentrations. MonAB CRC54 against GP IIb-IIIa, which induced its interaction with fibrinogen and platelet aggregation, also stimulated serotonin and P-selectin secretion. Both types of release reactions were completely suppressed by ReoPro and FRAMON. Aspirin, the cyclooxygenase inhibitor, also prevented CRC54-induced secretion, proving the dependence of this process on thromboxane A2 synthesis. Upon platelet activation by concanavalin A (Con A), caused by clusterization of membrane glycoproteins, GP IIb-IIIa blockade only slightly (by 15-20%) decreased serotonin secretion. High level of Con A-induced secretion was also detected in a patient with hereditary deficiency of GP IIb-IIIa. Thus, neither clusterization nor occupation of GP IIb-IIIa are essential for the stimulation of Con A-induced release reaction. The data indicate that GP IIb-IIIa binding with fibrinogen leads to the stimulation of secretion from platelet granules. When the level of secretion does not depend on GP IIb-IIIa interaction with the ligands or its presence on platelets full-scale release reaction is presumably stimulated by activating signals formed without GP IIb-IIIa involvement.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Clemetson, K. J. (1995) Thromb. Haemost., 74, 111-116.

    Google Scholar 

  2. Shatill, S. J., Kashiwagi, H., and Pampori, N. (1998) Blood, 91, 2645-2657.

    Google Scholar 

  3. Shatill, S. J. (1999) Thromb. Haemost., 82, 318-325.

    Google Scholar 

  4. Majerus, P. W. (2000) in The Molecular Basis of Blood Diseases (Stamatoyannopoulos, G., Majerus, P. W., Perlmutter, R. M., and Varmus, H., eds.) W. B. Sanders Company, Philadelphia-London-New York-St. Louis-Sydney-Toronto, pp. 764-790.

    Google Scholar 

  5. Byzova, T. V., Vlasik, T. N., and Mazurov, A. V. (1994) Byul. Eksp. Biol. Med., No. 10, 402-405.

    Google Scholar 

  6. Mazurov, A. V., Khaspekova, S. G., Byzova, T. V., Tikhomirov, O. Yu., Berndt, M. C., Steiner, B., and Kouns, W. C. (1996) FEBS Lett., 391, 84-88.

    Google Scholar 

  7. Mazurov, A. V., Pevzner, D. V., Khaspekova, S. G., Dudnik, O. A., Byzova, T. V., Vlasik, T. N., Bakharev, V. N., Piscov, M. Yu., Staroverov, I. I., and Ruda, M. Ya. (2001) Ter. Arkhiv, No. 9, 66-73.

    Google Scholar 

  8. Mazurov, A. V., Pevzner, D. V., Semenov, A. V., Antonova, O. A., Dudnik, O. A., Khaspekova, S. G., Vlasik, T. N., Samko, A. N., Staroverov, I. I., and Ruda, M. Ya. (2002) Kardiologiya, No. 6, 8-17.

    Google Scholar 

  9. Mazurov, A. V., Pevzner, D. V., Khaspekova, S. G., Byzova, T. V., Vlasik, T. N., Staroverov, I. I., Ruda, M. Ya., and Chazov, E. I. (2000) Platelets, 11, 356 (abstract).

    Google Scholar 

  10. Coller, B. S. (2001) Thromb. Haemost., 86, 427-443.

    Google Scholar 

  11. Topol, E. J., Byzova, T. V., and Plow, E. F. (1999) Lancet, 353, 227-231.

    Google Scholar 

  12. Khaspekova, S. G., Vlasik, T. N., Byzova, T. V., Vinogradov, D. V., Berndt, M. C., and Mazurov, A. V. (1993) Br. J. Haematol., 85, 332-340.

    Google Scholar 

  13. Smirnova, I. V., Khaspekova, S. G., Ignatov, V. V., and Mazurov, A. V. (1998) Biochemistry (Moscow), 63, 710-718.

    Google Scholar 

  14. Agafonova, O. G., Vinogradov, D. V., Khaspekova, S. G., Lagutina, N. Ya., Labinskaya, T. A., Vasil'ev, S. A., and Mazurov, A. V. (1992) Byul. Eksp. Biol. Med., No. 12, 635-637.

    Google Scholar 

  15. Semenov, A. V., Romanov, Yu. A., Loktionova, S. A., Tikhomirov, O. Yu., Khachikian, M. V., Vasil'ev, S. A., and Mazurov, A. V. (1999) Biochemistry (Moscow), 64, 1326-1335.

    Google Scholar 

  16. Patrono, C., Coller, B., Dalen, J. E., FitzGerald, G. A., Fuster, V., Gent, M., Hirsh, J., and Roth, G. (2001) Chest, 119(suppl), 39S-63S.

    Google Scholar 

  17. Santoro, S. A. (1983) Biochim. Biophys. Acta, 757, 101-110.

    Google Scholar 

  18. Ramaschi, G., Torti, M., Sinigaglia, F., and Balduini, C. (1993) Cell Biochem. Funct., 11, 241-249.

    Google Scholar 

  19. Torti, M., Festetics, E. T., Bertoni, A., Sinigaglia, F., and Balduini, C. (1999) Thromb. Haemost., 81, 124-130.

    Google Scholar 

  20. Kakaiya, R. M., Kiraly, T. L., and Cable, R. G. (1988) Thromb. Haemost., 59, 281-283.

    Google Scholar 

  21. Kariyazono, H., Nakamura, K., Shinkawa, T., Yamaguchi, T., Sakata, R., and Yamada, K. (2001) Thromb. Res., 101, 445-453.

    Google Scholar 

  22. Furie, B., and Furie, B. C. (1995) Thromb. Haemost., 74, 224-227.

    Google Scholar 

  23. Dunlop, L. C., Skinner, M. P., Bendall, L. J., Favaloro, E. J., Castaldi, P. A., Gorman, J. J., Gamble, J. R., Vadas, M. A., and Berndt, M. C. (1992) J. Exp. Med., 175, 1147-1150.

    Google Scholar 

  24. Ushiyama, S., Laue, T. M., Moore, K. L., Erickson, H. P., and McEver, R. P. (1993) J. Biol. Chem., 268, 15229-15237.

    Google Scholar 

  25. Frelinger, A. L., III, Du, X., Plow, E. F., and Ginsberg, M. H. (1991) J. Biol. Chem., 266, 17106-17111.

    Google Scholar 

  26. Kouns, W. C., Wall, C. D., White, M. M., Fox, C. F., and Jennings, L. K. (1990) J. Biol. Chem., 265, 20594-20601.

    Google Scholar 

  27. Kouns, W. C., Newman, P. J., Puckett, K. J., Miller, A. A., Wall, C. D., Fox, C. F., Seyer, J. M., and Jennings, L. K. (1991) Blood, 78, 3215-3223.

    Google Scholar 

  28. Kouns, W. C., and Jennings, L. K. (1991) Thromb. Res., 63, 343-354.

    Google Scholar 

  29. Chronos, N., Marciniak, S. J., and Nakada, M. T. (1999) Eur. Heart J., Suppl. 1 (Suppl. E), E11-E17.

    Google Scholar 

  30. Klinkhardt, U., Kirchmaier, C. M., Westrup, D., Breddin, H. K., Mahnel, R. G., Hild, M., and Harder, S. (2000) Thromb. Res., 97, 201-207.

    Google Scholar 

  31. Coller, B. S., Peerschke, E. I., Scudder, L. E., and Sullivan, C. A. (1983) J. Clin. Invest., 72, 325-338.

    Google Scholar 

  32. Carrol, R. C., Wang, X. L., Lanza, F., Steiner, B., and Kouns, W. C. (1997) Thromb. Res., 88, 109-125.

    Google Scholar 

  33. Malmsten, C., Kindahl, H., Samuelsson, B., Levy-Toledano, S., Tobelem, G., and Caen, J. P. (1977) Br. J. Haematol., 35, 511-520.

    Google Scholar 

  34. Tsao, P. W., Forsythe, M. S., and Mousa, S. A. (1997) Thromb. Res., 88, 137-146.

    Google Scholar 

  35. Schneider, D. J., Taatjes, D. J., and Sobel, B. E. (2000) Cardiovasc. Res., 45, 437-446.

    Google Scholar 

  36. Rossi, F., Rossi, E., Pareti, F. I., Colli, S., Tremoli, E., and Gallo, L. (2001) Hematologica, 86, 192-198.

    Google Scholar 

  37. Torti, M., Ramaschi G., Montsarrat, N., Sinigaglia, F., Balduini, C., Plantavid, M., Breton, M., Chap, H., and Mauco, G. (1995) J. Biol. Chem., 270, 13179-13185.

    Google Scholar 

  38. Le Breto, H., Plow, E. F., and Topol, E. J. (1996) J. Am. Coll. Cardiol., 28, 1643-1652.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Russian Cardiology Research Center, 3-ya Cherepkovskaya ul. 15a, Institute of Experimental Cardiology, Moscow, 121552, Russia

    Ya. A. Naimushin & A. V. Mazurov

Authors
  1. Ya. A. Naimushin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. V. Mazurov
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naimushin, Y.A., Mazurov, A.V. Role of Glycoprotein IIb-IIIa (αIIbβ3-integrin) in Stimulation of Secretion from Platelet Granules. Biochemistry (Moscow) 68, 209–216 (2003). https://doi.org/10.1023/A:1022605613859

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022605613859

Search

Navigation