TY - JOUR
T1 - Role of glycoprotein IbIalpha mobility in platelet function
AU - van der Wal, Evertdina
AU - Verhoef, Sandra
AU - Schutgens, Rober EG
AU - Peters, Marjolein
AU - Wu, Yaping
AU - Akkerman, Jan-Willem N
PY - 2010
Y1 - 2010
N2 - Incubation at 0A?C is known to expose I?-N-acetyl-D-glucosamine residues on glycoprotein (GP) IbI? inducing receptor clustering and I? MI? 2-mediated platelet destruction by macrophages. Here we show that incubation at 0/37A?C (4 hours at 0A?C, followed by 1 hour at 37A?C to mimic cold-storage and post-transfusion conditions) triggers a conformational change in the N-terminal flank (NTF, amino acids, aa 1-35) but not in aa 36-282 of GPIbI? as detected by antibody binding. Addition of the sugar N-acetyl-D-glucosamine (GN) inhibits responses induced by 0/37A?C. Incubation at 0A?C shifts GPIbI? from the membrane skeleton to the cytoskeleton. Different GPIbI? conformations have little effect on VWF/ristocetin-induced aggregation, but arrest of NTF change by GN interferes with agglutination and spreading on a VWF-coated surface under flow. Strikingly, incubation at 0/37A?C initiates thromboxane A 2 formation through a von Willebrand factor (VWF)-independent and GPIbI?-dependent mechanism, as confirmed in VWF- and GPIbI?-deficient platelets. We conclude that the NTF change induced by 0/37A?C incubation reflects clustering of GPIbI? supports VWF/ristocetin-induced agglutination and spreading and is sufficient to initiate platelet activation in the absence of VWF. A? Schattauer 2010.
AB - Incubation at 0A?C is known to expose I?-N-acetyl-D-glucosamine residues on glycoprotein (GP) IbI? inducing receptor clustering and I? MI? 2-mediated platelet destruction by macrophages. Here we show that incubation at 0/37A?C (4 hours at 0A?C, followed by 1 hour at 37A?C to mimic cold-storage and post-transfusion conditions) triggers a conformational change in the N-terminal flank (NTF, amino acids, aa 1-35) but not in aa 36-282 of GPIbI? as detected by antibody binding. Addition of the sugar N-acetyl-D-glucosamine (GN) inhibits responses induced by 0/37A?C. Incubation at 0A?C shifts GPIbI? from the membrane skeleton to the cytoskeleton. Different GPIbI? conformations have little effect on VWF/ristocetin-induced aggregation, but arrest of NTF change by GN interferes with agglutination and spreading on a VWF-coated surface under flow. Strikingly, incubation at 0/37A?C initiates thromboxane A 2 formation through a von Willebrand factor (VWF)-independent and GPIbI?-dependent mechanism, as confirmed in VWF- and GPIbI?-deficient platelets. We conclude that the NTF change induced by 0/37A?C incubation reflects clustering of GPIbI? supports VWF/ristocetin-induced agglutination and spreading and is sufficient to initiate platelet activation in the absence of VWF. A? Schattauer 2010.
UR - http://www.schattauer.de.ezproxy.lib.monash.edu.au/de/magazine/uebersicht/zeitschriften-a-z/thrombosis-and-haemostasis/contents/archive/issue/1069/man
U2 - 10.1160/TH09-11-0751
DO - 10.1160/TH09-11-0751
M3 - Article
VL - 103
SP - 1033
EP - 1043
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 5
ER -