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- W2550021721 abstract "Abstract For preservation of platelet concentrates, storage at 0°C might be superior to current storage procedures at 22°C since cold storage reduces bacterial growth and might better preserve platelet functions. A major problem is that cold damages the glycosylation of the von Willebrand Factor (VWF) receptor Glycoprotein (GP) Ib&alpha, exposing N-acetyl- D-glucosamine (GlcNAc) residues and inducing receptor clustering. We investigated the effect of dispersed and clustered conformations of GPIb-alpha on the haemostatic functions of the receptor. We deduced the glycosylation state from binding of succinylated wheat germ agglutinin (sWGA) and clustering from binding of AN-51 antibody directed against aa 1–35 which differed between dispersed and clustered GPIb-alpha. We compared different GPIb-alpha conformations with anchorage to the membrane- and cytoskeleton and VWF/ristocetin (VWF*)-induced platelet functions and confirmed specificity for GPIb-alpha and VWF effects by control studies in GPIb-alpha- and VWF-deficient platelets. VWF*- and cold-treatment released GPIb-alpha from the membrane skeleton, inducing sWGA-binding, clustering and anchorage to the cytoskeleton. Addition of GlcNAc restored dispersed GPIb-alpha after cold but not after VWF*-treatment. VWF*- induced aggregation and adhesion to coated VWF under flow were little affected by changes in GPIb-alpha conformation but agglutination, spreading and formation of stress fibers strongly depended on clustered GPIb-alpha. Following cold-induced clustering of GPIb-alpha subsequent incubation at 37°C triggered formation of thromboxane (Tx)A2 in a GPIb-alpha-dependent manner but independent of added or endogenous VWF. GlcNAc strongly inhibited VWF*-induced agglutination, spreading on coated VWF and VWF-independent TxA2 formation. We conclude that incubation at 0°C triggers clustering of GPIb-alpha which activates platelets independent of its ligand VWF." @default.
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- W2550021721 date "2008-11-16" @default.
- W2550021721 modified "2023-10-18" @default.
- W2550021721 title "Role of Glycoprotein Ibα Mobility in Platelet Function." @default.
- W2550021721 doi "https://doi.org/10.1182/blood.v112.11.1850.1850" @default.
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