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Thromb Haemost 2010; 103(05): 1033-1043
DOI: 10.1160/TH09-11-0751
Platelets and Blood Cells
Schattauer GmbH

Role of glycoprotein Ibα mobility in platelet function

Dianne E. van der Wal
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
,
Sandra Verhoef
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
,
Roger E. G. Schutgens
2   Department of Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
,
Marjolein Peters
3   Department of Pediatric-Haematology, Emma Childrens Hospital, Academic Medical Center Amsterdam
,
Yaping Wu
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
,
Jan Willem N. Akkerman
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 03 November 2009

Accepted after minor revision: 06 January 2010

Publication Date:
22 November 2017 (online)

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Summary

Incubation at 0°C is known to expose β-N-acetyl-D-glucosamine residues on glycoprotein (GP) Ibα inducing receptor clustering and αMβ2-mediated platelet destruction by macrophages. Here we show that incubation at 0/37°C (4 hours at 0°C, followed by 1 hour at 37°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 GPIbα as detected by antibody binding. Addition of the sugar N-acetyl-D-glucosamine (GN) inhibits responses induced by 0/37°C. Incubation at 0°C shifts GPIbα from the membrane skeleton to the cytoskeleton. Different GPIbα 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 0/37°C initiates thromboxane A2 formation through a von Willebrand factor (VWF)-independent and GPIbα-dependent mechanism, as confirmed in VWF- and GPIbαﺹdeficient platelets. We conclude that the NTF change induced by 0/37°C incubation reflects clustering of GPIbα supports VWF/ristocetin-induced agglutination and spreading and is sufficient to initiate platelet activation in the absence of VWF.

Keywords

Glycoprotein Ibα - cold-storage - cytoskeleton - platelet - thromboxane A2
 

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