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

D. Best, Y.A. Senis, Gavin Jarvis, H.J. Eagleton, D.J. Roberts, T. Saito, S.M. Jung, M. Moroi, P. Harrison, F.R. Green, S.P. Watson

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)2811-2818
Number of pages8
JournalBlood
Volume102
Issue number8
DOIs
Publication statusPublished - 15 Oct 2003

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Platelets
Glycoproteins
Blood Platelets
IgG Receptors
Myeloproliferative Disorders
Thrombosis
Collagen
Immunoreceptor Tyrosine-Based Activation Motif
Collagen Receptors
Homozygote
Serine
Polymorphism
Tyrosine
Alleles
Genotype
Blood
Genes
Chemical activation
Control Groups

Cite this

Best, D., Senis, Y. A., Jarvis, G., Eagleton, H. J., Roberts, D. J., Saito, T., ... Watson, S. P. (2003). GPVI levels in platelets: relationship to platelet function at high shear. Blood, 102(8), 2811-2818. https://doi.org/10.1182/blood-2003-01-0231
Best, D. ; Senis, Y.A. ; Jarvis, Gavin ; Eagleton, H.J. ; Roberts, D.J. ; Saito, T. ; Jung, S.M. ; Moroi, M. ; Harrison, P. ; Green, F.R. ; Watson, S.P. / GPVI levels in platelets: relationship to platelet function at high shear. In: Blood. 2003 ; Vol. 102, No. 8. pp. 2811-2818.
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Best, D, Senis, YA, Jarvis, G, Eagleton, HJ, Roberts, DJ, Saito, T, Jung, SM, Moroi, M, Harrison, P, Green, FR & Watson, SP 2003, 'GPVI levels in platelets: relationship to platelet function at high shear', Blood, vol. 102, no. 8, pp. 2811-2818. https://doi.org/10.1182/blood-2003-01-0231

GPVI levels in platelets: relationship to platelet function at high shear. / Best, D.; Senis, Y.A.; Jarvis, Gavin; Eagleton, H.J.; Roberts, D.J.; Saito, T.; Jung, S.M.; Moroi, M.; Harrison, P.; Green, F.R.; Watson, S.P.

In: Blood, Vol. 102, No. 8, 15.10.2003, p. 2811-2818.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GPVI levels in platelets: relationship to platelet function at high shear

AU - Best, D.

AU - Senis, Y.A.

AU - Jarvis, Gavin

AU - Eagleton, H.J.

AU - Roberts, D.J.

AU - Saito, T.

AU - Jung, S.M.

AU - Moroi, M.

AU - Harrison, P.

AU - Green, F.R.

AU - Watson, S.P.

PY - 2003/10/15

Y1 - 2003/10/15

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2003-01-0231

DO - 10.1182/blood-2003-01-0231

M3 - Article

VL - 102

SP - 2811

EP - 2818

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -

Best D, Senis YA, Jarvis G, Eagleton HJ, Roberts DJ, Saito T et al. GPVI levels in platelets: relationship to platelet function at high shear. Blood. 2003 Oct 15;102(8):2811-2818. https://doi.org/10.1182/blood-2003-01-0231