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. 2000 Jun;78(6):2834–2843. doi: 10.1016/S0006-3495(00)76826-3

Efficiency of platelet adhesion to fibrinogen depends on both cell activation and flow.

A Bonnefoy 1, Q Liu 1, C Legrand 1, M M Frojmovic 1
PMCID: PMC1300871  PMID: 10827966

Abstract

The kinetics of adhesion of platelets to fibrinogen (Fg) immobilized on polystyrene latex beads (Fg-beads) was determined in suspensions undergoing Couette flow at well-defined homogeneous shear rates. The efficiency of platelet adhesion to Fg-beads was compared for ADP-activated versus "resting" platelets. The effects of the shear rate (100-2000 s(-1)), Fg density on the beads (24-2882 Fg/microm(2)), the concentration of ADP used to activate the platelets, and the presence of soluble fibrinogen were assessed. "Resting" platelets did not specifically adhere to Fg-beads at levels detectable with our methodology. The apparent efficiency of platelet adhesion to Fg-beads readily correlated with the proportion of platelets "quantally" activated by doses of ADP, i.e., only ADP-activated platelets appeared to adhere to Fg-beads, with a maximal adhesion efficiency of 6-10% at shear rates of 100-300 s(-1), decreasing with increasing shear rates up to 2000 s(-1). The adhesion efficiency was found to decrease by only threefold when decreasing the density of Fg at the surface of the beads by 100-fold, with only moderate decreases in the presence of physiologic concentrations of soluble Fg. These adhesive interactions were also compared using activated GPIIbIIIa-coated beads. Our studies provide novel model particles for studying platelet adhesion relevant to hemostasis and thrombosis, and show how the state of activation of the platelet and the local flow conditions regulate Fg-dependent adhesion.

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Selected References

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  1. Alig L., Edenhofer A., Hadváry P., Hürzeler M., Knopp D., Müller M., Steiner B., Trzeciak A., Weller T. Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem. 1992 Nov 13;35(23):4393–4407. doi: 10.1021/jm00101a017. [DOI] [PubMed] [Google Scholar]
  2. Bennett J. S., Vilaire G., Cines D. B. Identification of the fibrinogen receptor on human platelets by photoaffinity labeling. J Biol Chem. 1982 Jul 25;257(14):8049–8054. [PubMed] [Google Scholar]
  3. Bennett J. S., Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest. 1979 Nov;64(5):1393–1401. doi: 10.1172/JCI109597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bini A., Kudryk B. J. Fibrinogen in human atherosclerosis. Ann N Y Acad Sci. 1995 Jan 17;748:461–473. doi: 10.1111/j.1749-6632.1994.tb17342.x. [DOI] [PubMed] [Google Scholar]
  5. Born G. V., Richardson P. D. Activation time of blood platelets. J Membr Biol. 1980 Dec 15;57(2):87–90. doi: 10.1007/BF01868994. [DOI] [PubMed] [Google Scholar]
  6. Endenburg S. C., Lindeboom-Blokzijl L., Zwaginga J. J., Sixma J. J., de Groot P. G. Plasma fibrinogen inhibits platelets adhesion in flowing blood to immobilized fibrinogen. Arterioscler Thromb Vasc Biol. 1996 May;16(5):633–638. doi: 10.1161/01.atv.16.5.633. [DOI] [PubMed] [Google Scholar]
  7. Farrell D. H., Thiagarajan P., Chung D. W., Davie E. W. Role of fibrinogen alpha and gamma chain sites in platelet aggregation. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10729–10732. doi: 10.1073/pnas.89.22.10729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frenette P. S., Johnson R. C., Hynes R. O., Wagner D. D. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7450–7454. doi: 10.1073/pnas.92.16.7450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frojmovic M. M., Kasirer-Friede A., Goldsmith H. L., Brown E. A. Surface-secreted von Willebrand factor mediates aggregation of ADP-activated platelets at moderate shear stress: facilitated by GPIb but controlled by GPIIb-IIIa. Thromb Haemost. 1997 Mar;77(3):568–576. [PubMed] [Google Scholar]
  10. Frojmovic M. M., Mooney R. F., Wong T. Dynamics of platelet glycoprotein IIb-IIIa receptor expression and fibrinogen binding. II. Quantal activation parallels platelet capture in stir-associated microaggregation. Biophys J. 1994 Nov;67(5):2069–2075. doi: 10.1016/S0006-3495(94)80690-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frojmovic M., Wong T., van de Ven T. Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. I. Methodology, theory and results for two distinct activators. Biophys J. 1991 Apr;59(4):815–827. doi: 10.1016/S0006-3495(91)82294-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furie B., Furie B. C. The molecular basis of blood coagulation. Cell. 1988 May 20;53(4):505–518. doi: 10.1016/0092-8674(88)90567-3. [DOI] [PubMed] [Google Scholar]
  13. Gartner T. K., Amrani D. L., Derrick J. M., Kirschbaum N. E., Matsueda G. R., Taylor D. B. Characterization of adhesion of "resting" and stimulated platelets to fibrinogen and its fragments. Thromb Res. 1993 Jul 1;71(1):47–60. doi: 10.1016/0049-3848(93)90204-2. [DOI] [PubMed] [Google Scholar]
  14. Gear A. R. Platelet adhesion, shape change, and aggregation: rapid initiation and signal transduction events. Can J Physiol Pharmacol. 1994 Mar;72(3):285–294. doi: 10.1139/y94-044. [DOI] [PubMed] [Google Scholar]
  15. Goldsmith H. L., Bell D. N., Braovac S., Steinberg A., McIntosh F. Physical and chemical effects of red cells in the shear-induced aggregation of human platelets. Biophys J. 1995 Oct;69(4):1584–1595. doi: 10.1016/S0006-3495(95)80031-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goldsmith H. L., Frojmovic M. M., Braovac S., McIntosh F., Wong T. Adenosine diphosphate-induced aggregation of human platelets in flow through tubes: III. Shear and extrinsic fibrinogen-dependent effects. Thromb Haemost. 1994 Jan;71(1):78–90. [PubMed] [Google Scholar]
  17. Hatton M. W., Moar S. L., Richardson M. Deendothelialization in vivo initiates a thrombogenic reaction at the rabbit aorta surface. Correlation of uptake of fibrinogen and antithrombin III with thrombin generation by the exposed subendothelium. Am J Pathol. 1989 Sep;135(3):499–508. [PMC free article] [PubMed] [Google Scholar]
  18. Hawiger J. Adhesive ends of fibrinogen and its antiadhesive peptides: the end of a saga? Semin Hematol. 1995 Apr;32(2):99–109. [PubMed] [Google Scholar]
  19. Liu Q., Matsueda G., Brown E., Frojmovic M. The AGDV residues on the gamma chain carboxyl terminus of platelet-bound fibrinogen are needed for platelet aggregation. Biochim Biophys Acta. 1997 Dec 5;1343(2):316–326. doi: 10.1016/s0167-4838(97)00130-1. [DOI] [PubMed] [Google Scholar]
  20. Liu Q., Rooney M. M., Kasirer-Friede A., Brown E., Lord S. T., Frojmovic M. M. Role of the gamma chain Ala-Gly-Asp-Val and Aalpha chain Arg-Gly-Asp-Ser sites of fibrinogen in coaggregation of platelets and fibrinogen-coated beads. Biochim Biophys Acta. 1998 Jun 11;1385(1):33–42. doi: 10.1016/s0167-4838(98)00039-9. [DOI] [PubMed] [Google Scholar]
  21. Lüscher E. F., Weber S. The formation of the haemostatic plug--a special case of platelet aggregation. An experiment and a survey of the literature. Thromb Haemost. 1993 Aug 2;70(2):234–237. [PubMed] [Google Scholar]
  22. Marchant R. E., Barb M. D., Shainoff J. R., Eppell S. J., Wilson D. L., Siedlecki C. A. Three dimensional structure of human fibrinogen under aqueous conditions visualized by atomic force microscopy. Thromb Haemost. 1997 Jun;77(6):1048–1051. [PubMed] [Google Scholar]
  23. Marguerie G. A., Plow E. F., Edgington T. S. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem. 1979 Jun 25;254(12):5357–5363. [PubMed] [Google Scholar]
  24. Munn L. L., Melder R. J., Jain R. K. Role of erythrocytes in leukocyte-endothelial interactions: mathematical model and experimental validation. Biophys J. 1996 Jul;71(1):466–478. doi: 10.1016/S0006-3495(96)79248-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peerschke E. I. The platelet fibrinogen receptor. Semin Hematol. 1985 Oct;22(4):241–259. [PubMed] [Google Scholar]
  26. Plow E. F., Ginsberg M. H. Cellular adhesion: GPIIb-IIIa as a prototypic adhesion receptor. Prog Hemost Thromb. 1989;9:117–156. [PubMed] [Google Scholar]
  27. Plow E. F., Marguerie G. A. Induction of the fibrinogen receptor on human platelets by epinephrine and the combination of epinephrine and ADP. J Biol Chem. 1980 Nov 25;255(22):10971–10977. [PubMed] [Google Scholar]
  28. Polanowska-Grabowska R., Simon C. G., Jr, Gear A. R. Platelet adhesion to collagen type I, collagen type IV, von Willebrand factor, fibronectin, laminin and fibrinogen: rapid kinetics under shear. Thromb Haemost. 1999 Jan;81(1):118–123. [PubMed] [Google Scholar]
  29. Raha S., Jones G. D., Gear A. R. Sub-second oscillations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate during platelet activation by ADP and thrombin: lack of correlation with calcium kinetics. Biochem J. 1993 Jun 15;292(Pt 3):643–646. doi: 10.1042/bj2920643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ruggeri Z. M. New insights into the mechanisms of platelet adhesion and aggregation. Semin Hematol. 1994 Jul;31(3):229–239. [PubMed] [Google Scholar]
  31. Sage S. O., Merritt J. E., Hallam T. J., Rink T. J. Receptor-mediated calcium entry in fura-2-loaded human platelets stimulated with ADP and thrombin. Dual-wavelengths studies with Mn2+. Biochem J. 1989 Mar 15;258(3):923–926. doi: 10.1042/bj2580923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Savage B., Bottini E., Ruggeri Z. M. Interaction of integrin alpha IIb beta 3 with multiple fibrinogen domains during platelet adhesion. J Biol Chem. 1995 Dec 1;270(48):28812–28817. doi: 10.1074/jbc.270.48.28812. [DOI] [PubMed] [Google Scholar]
  33. Savage B., Saldívar E., Ruggeri Z. M. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell. 1996 Jan 26;84(2):289–297. doi: 10.1016/s0092-8674(00)80983-6. [DOI] [PubMed] [Google Scholar]
  34. Shiba E., Lindon J. N., Kushner L., Matsueda G. R., Hawiger J., Kloczewiak M., Kudryk B., Salzman E. W. Antibody-detectable changes in fibrinogen adsorption affecting platelet activation on polymer surfaces. Am J Physiol. 1991 May;260(5 Pt 1):C965–C974. doi: 10.1152/ajpcell.1991.260.5.C965. [DOI] [PubMed] [Google Scholar]
  35. Taatjes D. J., Quinn A. S., Jenny R. J., Hale P., Bovill E. G., McDonagh J. Tertiary structure of the hepatic cell protein fibrinogen in fluid revealed by atomic force microscopy. Cell Biol Int. 1997 Nov;21(11):715–726. doi: 10.1006/cbir.1997.0216. [DOI] [PubMed] [Google Scholar]
  36. Tandon P., Diamond S. L. Hydrodynamic effects and receptor interactions of platelets and their aggregates in linear shear flow. Biophys J. 1997 Nov;73(5):2819–2835. doi: 10.1016/S0006-3495(97)78311-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wong T., Pedvis L., Frojmovic M. Platelet size affects both micro- and macro-aggregation: contributions of platelet number, volume fraction and cell surface. Thromb Haemost. 1989 Sep 29;62(2):733–741. [PubMed] [Google Scholar]
  38. Xia Z., Frojmovic M. M. Aggregation efficiency of activated normal or fixed platelets in a simple shear field: effect of shear and fibrinogen occupancy. Biophys J. 1994 Jun;66(6):2190–2201. doi: 10.1016/S0006-3495(94)81015-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Xia Z., Goldsmith H. L., van de Ven T. G. Kinetics of specific and nonspecific adhesion of red blood cells on glass. Biophys J. 1993 Sep;65(3):1073–1083. doi: 10.1016/S0006-3495(93)81178-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Xia Z., Wong T., Liu Q., Kasirer-Friede A., Brown E., Frojmovic M. M. Optimally functional fluorescein isothiocyanate-labelled fibrinogen for quantitative studies of binding to activated platelets and platelet aggregation. Br J Haematol. 1996 Apr;93(1):204–214. doi: 10.1046/j.1365-2141.1996.445980.x. [DOI] [PubMed] [Google Scholar]
  41. Xia Z., Woo L., van de Ven T. G. Microrheological aspects of adhesion of Escherichia coli on glass. Biorheology. 1989;26(2):359–375. doi: 10.3233/bir-1989-26219. [DOI] [PubMed] [Google Scholar]
  42. Zaidi T. N., McIntire L. V., Farrell D. H., Thiagarajan P. Adhesion of platelets to surface-bound fibrinogen under flow. Blood. 1996 Oct 15;88(8):2967–2972. [PubMed] [Google Scholar]

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