Download PDF
Thromb Haemost 2002; 88(03): 510-516
DOI: 10.1055/s-0037-1613245
Review Article
Schattauer GmbH

Collagen Response and Glycoprotein VI Function Decline Progressively as Canine Platelets Age in vivo

L. Alberio
1   Department of Medicine, W. K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
,
P. Friese
1   Department of Medicine, W. K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
,
K. J. Clemetson
2   Theodor Kocher Institute, University of Berne, Berne, Switzerland
,
G. L. Dale
1   Department of Medicine, W. K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
› Author Affiliations
Further Information

Publication History

Received 14 November 2001

Accepted after resubmission 06 May 2002

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Clinical and experimental observations suggest that platelet function deteriorates quickly with cell age. However, efforts to define agedependent alterations have detected only modest biochemical changes occurring late in the cell life span. In this report, we demonstrate two significant alterations of the collagen response occurring during in vivo aging of canine platelets: a progressive increase in the EC50 for collagen types I, III and V and the emergence of a population of aged platelets which are refractory to collagen. Experiments with convulxin, a specific agonist for the collagen receptor glycoprotein VI (GPVI), also demonstrate an age-dependent decline in activation and the appearance of a non-reactive, aged population as observed with native collagens. Our studies indicate that canine platelets have two distinct binding levels for FITC-labeled convulxin and that the higher binding level disappears upon cell aging. During these studies one dog (#428) was identified whose platelets not only failed to demonstrate an age-dependent decrease in convulxin reactivity but also maintained a high convulxinbinding ability throughout their otherwise normal life span. Transfusion of biotinylated platelets from control dogs into dog #428 showed that the expected changes in collagen response and GPVI function did not occur in the transfused platelets. These observations demonstrate that the canine platelet response towards collagen is strongly dependent upon cell-age and suggest that this functional decline is at least partly due to an extrinsic-mediated alteration, possibly proteolytic, of GPVI.

This work was supported in part by grants HL53585 and HL68129 from the National Institutes of Health (GLD) and the Swiss National Science Foundation (SSMBS grant, LA; grant 31-52396.97, KJC). This work has been presented at the XVIII Congress of the International Society on Thrombosis and Haemostasis (Paris, 2001).

Keywords

Platelets - collagen - cell-age - P-selectin - flow-cytometry - convulxin - glycoprotein VI
 

  • References

  • 1 Wright HP. Changes in the adhesiveness of blood platelets following parturition and surgical operations. J Pathol Bacteriol 1942; 54: 461-8.
    CrossrefPubMedGoogle Scholar
  • 2 Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 1972; 287: 155-9.
    CrossrefPubMedGoogle Scholar
  • 3 Lacey JV, Penner JA. Management of idiopathic thrombocytopenic purpura in the adult. Sem Thromb Hemost 1977; 03: 160-74.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Thompson CB, Jakubowski JA, Quinn PG, Deykin D, Valeri CR. Platelet size and age determine platelet function independently. Blood 1984; 63: 1372-5.
    PubMedGoogle Scholar
  • 5 Hirsh J, Glynn MF, Mustard JF. The effect of platelet age on platelet adherence to collagen. J Clin Invest 1968; 47: 466-73.
    CrossrefPubMedGoogle Scholar
  • 6 Imbach P. Immune thrombocytopenia in children: The immune character of destructive thrombocytopenia and the treatment of bleeding. Sem Thromb Hemost 1995; 21: 305-12.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Dale GL. Platelet turnover. In: Thrombosis and Hemorrhage. Loscalzo J, Schafer AI. eds. Baltimore: Williams & Wilkins; 1998: 195-205.
    Google Scholar
  • 8 Heilmann E, Friese P, Anderson S, George JN, Hanson SR, Burstein SA, Dale GL. Biotinylated platelets: A new approach to the measurement of platelet life span. Br J Haematol 1993; 85: 729-35.
    CrossrefPubMedGoogle Scholar
  • 9 Dale GL, Friese P, Hynes LA, Burstein SA. Demonstration that thiazole orange-positive platelets in the dog are less than twenty-four hours old. Blood 1995; 85: 1822-5.
    PubMedGoogle Scholar
  • 10 Ault KA, Knowles C. In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation. Exp Hematol 1995; 23: 996-1001.
    PubMedGoogle Scholar
  • 11 Peng J, Friese P, Heilmann E, George JN, Burstein SA, Dale GL. Aged platelets have an impaired response to thrombin as quantitated by P-selectin expression. Blood 1994; 83: 161-6.
    PubMedGoogle Scholar
  • 12 Kehrel B. Platelet-collagen interactions. Sem Thromb Hemost 1995; 21: 123-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Saelman EUM, Nieuwenhuis HK, Hese KM, De Groot PG, Heijnen HFG, Sage EH, Williams S, McKeown L, Gralnick HR, Sixma JJ. Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (α2β1-integrin). Blood 1994; 83: 1244-50.
    PubMedGoogle Scholar
  • 14 Kehrel B, Wierwille S, Clemetson KJ, Anders O, Steiner M, Knight CG, Farndale RW, Okuma M, Barnes MJ. Glycoprotein VI is a major collagen receptor for platelet activation: It recognizes the platelet activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa and von Willebrand factor do not. Blood 1998; 91: 491-9.
    PubMedGoogle Scholar
  • 15 Tandon NN, Kralisz U, Jamieson GA. Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. J Biol Chem 1989; 264: 7576-83.
    PubMedGoogle Scholar
  • 16 Chiang TM, Rinaldy A, Kang AH. Cloning, characterization, and functional studies of a nonintegrin platelet receptor for type I collagen. J Clin Invest 1997; 100: 514-21.
    CrossrefPubMedGoogle Scholar
  • 17 Nieuwenhuis HK, Akkerman JW, Houdijk WPW, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985; 318: 470-2.
    CrossrefPubMedGoogle Scholar
  • 18 Moroi M, Jung SM. Platelet receptors for collagen. Thromb Haemost 1997; 78: 439-44.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Keely PJ, Parise LV. The α2β1 integrin is a necessary co-receptor for collagen-induced activation of Syk and the subsequent phosphorylation of phospholipase Cgamma2 in platelets. J Biol Chem 1996; 271: 26668-76.
    CrossrefPubMedGoogle Scholar
  • 20 Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R, Lindhout T, Heemskerk JW, Zirngibl H, Fassler R. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 5-1-2001; 20: 2120-30.
    PubMedGoogle Scholar
  • 21 Teng CM, Ko FN, Tsai IH, Hung ML, Huang TF. Trimucytin: A collagenlike aggregating inducer isolated from Trimeresurus mucrosquamatus snake venom. Thromb Haemost 1993; 69: 286-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Huang TF, Liu CZ, Yang SH. Aggretin, a novel platelet aggregation inducer from snake (Calloselasma rhodostoma) venom, activates phospholipase C by acting as a glycoprotein IaIIa agonist. Biochem J 1995; 309: 1021-7.
    CrossrefPubMedGoogle Scholar
  • 23 Polgar J, Clemetson JM, Kehrel BE, Wiedemann M, Magnenat EM, Wells TNC, Clemetson KJ. Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J Biol Chem 1997; 272: 13576-83.
    CrossrefPubMedGoogle Scholar
  • 24 Jandrot-Perrus M, Lagrue AH, Okuma M, Bon C. Adhesion and activation of human platelets induced by convulxin involve glycoprotein VI and integrin alpha2beta1. J Biol Chem 1997; 272: 27035-41.
    CrossrefPubMedGoogle Scholar
  • 25 Francischetti IMB, Ghazaleh FA, Reis RAM, Carlini CR, Guimaraes JA. Convulxin induces platelet activation by a tyrosine-kinase-dependent pathway and stimulates tyrosine phosphorylation of platelet proteins, including PLCgamma2, independently of integrin αIIbβ3 . Arch Biochem Biophys 1998; 353: 239-50.
    CrossrefPubMedGoogle Scholar
  • 26 Ezumi Y, Shindoh K, Tsuji M, Takayama H. Physical and functional association of the Src family kinases Fyn and Lyn with the collagen receptor glycoprotein VI-Fc receptor gamma chain complex on human platelets. J Exp Med 1998; 188: 267-76.
    CrossrefPubMedGoogle Scholar
  • 27 Clemetson JM, Polgar J, Magnenat E, Wells TNC, Clemetson KJ. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to Fc(alpha)R and the natural killer receptors. J Biol Chem 1999; 274: 29019-24.
    CrossrefPubMedGoogle Scholar
  • 28 Alberio L, Dale GL. Flow cytometric analysis of platelet activation by different collagen types present in the vessel wall. Br J Haematol 1998; 102: 1212-8.
    CrossrefPubMedGoogle Scholar
  • 29 Peng J, Friese P, Wolf RF, Harrison P, Downs T, Lok S, Dale GL, Burstein SA. Relative reactivity of platelets from thrombopoietin-and interleukin-6-treated dogs. Blood 1996; 87: 4158-63.
    PubMedGoogle Scholar
  • 30 Bellucci S, Monnet E, Lagrue AH, Boval B, Hainaud P, Robert A, Drouet L, Najman A, Fauvel F, Jandrot-Perrus M. A defective GPVI mediated signalling pathway, in a patient with myelodysplasia, is responsible for a lack of platelet activation response to types I and III collagens. Thromb Haemost 2001; 86S: A1793
    PubMedGoogle Scholar
  • 31 Ichinohe T, Takayama H, Ezumi Y, Arai M, Yamamoto N, Takahashi H, Okuma M. Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI. J Biol Chem 1997; 272: 63-8.
    CrossrefPubMedGoogle Scholar
  • 32 Alberio L, Safa O, Clemetson KJ, Esmon CT, Dale GL. Surface expression and functional characterization of alpha-granule factor V in human platelets: Effects of ionophore A23187, thrombin, collagen and convulxin. Blood 2000; 95: 1694-702.
    CrossrefPubMedGoogle Scholar
  • 33 Furihata K, Clemetson KJ, Deguchi H, Kunicki TJ. Variation in human platelet GPVI content modulates GPVI-specific prothrombinase activity. Arterioscler Thromb Vasc Biol 2001; 21: 1857-63.
    CrossrefPubMedGoogle Scholar