Abstract

P1300 Variation of GPVI levels in platelets: relationship to platelet function at high shear NIA Exhibition Area 09:30 16th July, 2003 Session Type: Posters Subject area: Receptors for primary agonists Session title: Platelet glycoproteins Abstract: P1300 Authors: D. Best*, Y. A. Senis+, G. E. Jarvis+, T. Saito‡, S. M. Jung‡, M. Moroi‡, P. Harrison+, F. R. Green+ & S. P. Watson+ *University of Oxford, UK; +UK; ‡Japan The interaction of platelet receptors with subendothelial components such as collagen is important in platelet adhesion and activation in response to blood vessel damage. There are at least two receptors which mediate the direct platelet-collagen interaction, the integrin GPIa-IIa and GPVI. We have examined the density of GPVI on human platelets from 102 volunteers and its relationship to dimorphisms within the GPVI promoter region (-154C/T) and the coding region T13254C which predicts a serine to proline substitution. In addition we have compared receptor levels to platelet adhesion under flow. GPVI levels varied 1.5-fold and showed a weak correlation (R2 = 0.12) with the levels of GPIa-IIa which varied threefold. Platelets from patients with the myeloproliferative disorders (MPD) essential thrombocythemia (ET) and polycythemia rubra vera (PRV) have significantly decreased levels of GPVI and GPIa-IIa. GPVI genotype had a significant effect on receptor expression with the high frequency 219 Ser/Ser having a 10% greater level than the less common 219 Ser/Pro (there were too few 219 Pro/Pro donors to reach a conclusion for this genotype) with no additional contribution from -154 C/T. Platelet function was assessed in a PFA-100 analyzer which measures platelet plug formation on a collagen-coated surface under shear and in murine platelets flowed on a collagen-coated surface. In both the normal and MPD groups GPVI levels had no effect on PFA-100 closure times. Similarly, murine platelets that express up to fivefold lower levels of GPVI than controls were able to form a thrombus on a high density collagen-coated surface whilst platelets lacking GPVI or a functional FcR gamma-chain exhibited abrogated thrombus formation at both 800/s and 1500/s. These results demonstrate that GPVI levels are tightly controlled and play a critical role in collagen adhesion but that a wide range of receptor density is sufficient to support platelet function under flow. This work was supported by the British Heart Foundation. file:///E|/working/LAXMI-PRASAD/WileyML-3G/deepak/31-Jan/Wednesday/Abstract%20P1300.html (1 of 2) [1/31/2014 3:50:56 PM]