GPVI levels in platelets: relationship to platelet function at high shear

被引:106
作者
Best, D
Senis, YA
Jarvis, GE
Eagleton, HJ
Roberts, DJ
Saito, T
Jung, SM
Moroi, M
Harrison, P
Green, FR
Watson, SP
机构
[1] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
[2] Univ Birmingham, Div Med Sci, Birmingham, W Midlands, England
[3] John Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England
[4] John Radcliffe Hosp, Natl Blood Serv Oxford Ctr, Oxford OX3 9DU, England
[5] Chiba Univ, Grad Sch Med, Dept Mol Genet, Chiba, Japan
[6] Riken Ctr Allergy & Immunol, Lab Cell Signalling, Yokohama, Kanagawa, Japan
[7] Kurume Univ, Inst Life Sci, Dept Prot Biochem, Kurume, Fukuoka 830, Japan
[8] Churchill Hosp, Oxford Haemophilia Ctr, Oxford OX3 7LJ, England
[9] Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England
关键词
D O I
10.1182/blood-2003-01-0231
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have investigated the density of the collagen receptors glycoprotein VI (GPVI) and alpha(2)beta(1) on human platelets and their relationship to polymorphisms within the GPVI gene. GPVI levels varied 1.5-fold and showed a weak correlation (r = 0.35) with the levels of alpha(2)beta(1), which varied 3-fold. GPVI genotype had a significant effect on receptor levels with carriers of the proline 219 allele (approximately 22% of the population) having 10% lower GPVI levels than the more common serine homozygotes. GPVI and alpha(2)beta(1) levels were found to be significantly decreased on platelets from patients with myeloproliferative disorders (MPDs). In both the MPD and the control group, GPVI levels were found not to affect platelet function under high shear in whole blood. Similarly murine platelets that express up to 5-fold lower levels of GPVI showed no significant difference than controls in thrombus formation on a high-density collagen-coated surface. However platelets lacking the GPVI/Fc receptor gamma-chain (FcR gamma-chain) complex or a functional FcR gamma-chain (immunoreceptor tyrosine-based activation motif [ITAM] point mutant) exhibited severely abrogated thrombus formation at 800 s(-1) and 1500 s(-1). These results demonstrate that GPVI levels are tightly controlled and play a critical role in thrombus formation on collagen; nevertheless, a range of receptor densities can support platelet function under high shear. (C) 2003 by The American Society of Hematology.
引用
收藏
页码:2811 / 2818
页数:8
相关论文
共 55 条
  • [11] Low platelet α2β1 levels in type I von Willebrand disease correlate with impaired platelet function in a high shear stress system
    Di Paola, J
    Federici, AB
    Mannucci, PM
    Canciani, FT
    Kritzik, M
    Kunicki, TJ
    Nugent, D
    [J]. BLOOD, 1999, 93 (11) : 3578 - 3582
  • [12] An intronic polyrnorphism in the PAR-1 gene is associated with platelet receptor density and the response to SFLLRN
    Dupont, A
    Fontana, P
    Bachelot-Loza, C
    Reny, JL
    Bièche, I
    Desvard, F
    Aiach, M
    Gaussem, P
    [J]. BLOOD, 2003, 101 (05) : 1833 - 1840
  • [13] FABRIS F, 1989, HAEMATOLOGICA, V74, P39
  • [14] Characterization of human glycoprotein VI gene 5′ regulatory and promoter regions
    Furihata, K
    Kunicki, TJ
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (10) : 1733 - 1739
  • [15] Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity
    Furihata, K
    Clemetson, KJ
    Deguchi, H
    Kunicki, TJ
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2001, 21 (11) : 1857 - 1863
  • [16] Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions
    Goto, SY
    Tamura, N
    Handa, S
    Arai, M
    Kodama, K
    Takayama, H
    [J]. CIRCULATION, 2002, 106 (02) : 266 - 272
  • [17] HANDA M, 1995, THROMB HAEMOSTASIS, V73, P521
  • [18] Performance of the platelet function analyser PFA-100® in testing abnormalities of primary haemostasis
    Harrison, P
    Robinson, MSC
    Mackie, IJ
    Joseph, J
    McDonald, SJ
    Liesner, R
    Savidge, GF
    Pasi, J
    Machin, SJ
    [J]. BLOOD COAGULATION & FIBRINOLYSIS, 1999, 10 (01) : 25 - 31
  • [19] Genetic variants of the hemostatic system and development of transplant coronary artery disease
    He, JQ
    Gaur, LK
    Stempien-Otero, A
    Nelson, K
    Levy, WC
    O'Brien, KD
    Bolgiano, DC
    Reiner, AP
    [J]. JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2002, 21 (06) : 629 - 636
  • [20] Integrin α2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen
    Holtkötter, O
    Nieswandt, B
    Smyth, N
    Müller, W
    Hafner, M
    Schulte, V
    Krieg, T
    Eckes, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) : 10789 - 10794