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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-01-0231.
Submitted January 28, 2003
Accepted June 6, 2003
GPVI levels in platelets: relationship to platelet function at high shear
Denise Best*, Yotis A Senis, Gavin E Jarvis, Helen J Eagleton, David J Roberts, Takashi Saito, Stephanie M Jung, Masaaki Moroi, Paul Harrison, Fiona R Green, and Steve P Watson
Department of Pharmacology, Oxford University, Oxford, United Kingdom
Department of Haematology, The John Radcliffe Hospital, Oxford, United Kingdom
National Blood Service-Oxford Centre, The John Radcliffe Hospital, Oxford, United Kingdom
Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba, Japan; Laboratory of Cell Signalling, Riken Centre for Allergy and Immunology, Yokahama, Japan
Department of Protein Biochemistry, Institute of Life Sciences Kurume University, Kurume, Japan
Oxford Haemophilia Centre, The Churchill Hospital, Oxford, United Kingdom
Department of Cardiovascular Medicine, Wellcome Trust Center for Human Genetics, Oxford, United Kingdom
Division of Medical Sciences, Birmingham University Medical School, Birmingham, United Kingdom; Department of Pharmacology, Oxford University, Oxford, United Kingdom
* Corresponding author; email: denise.best{at}pharmacology.ox.ac.uk.
We have investigated the density of the collagen receptors GPVI and  2 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 21 which varied three-fold. GPVI genotype had a significant effect on receptor levels with carriers of the proline 219 allele (~22% of the population) having 10% lower GPVI levels than the more common serine homozygotes. GPVI and 21 levels were found to be significantly decreased on platelets from patients with myeloproliferative disorders (MPD). 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 fivefold lower levels of GPVI showed no significant difference to controls in thrombus formation on a high density collagen-coated surface. However platelets lacking the GPVI/ FcR  -chain complex or a functional FcR -chain (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.
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