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Platelet apoptosis by cld-induced glycoportein Ibα clustering

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  • Dianne E van der Wal, Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Holland
  • V X Du, Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Holland
  • KS Lo, Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Holland
  • Jan Trige Rasmussen
  • S Verhoef, Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Holland
  • J W N Akkerman, Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Holland
Summary
Background: 
Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα-distribution indicative of receptor clustering and initiates thromboxane A2-formation. GPIbα is associated with 14-3-3 proteins, which contribute to GPIbα-signaling and in nucleated cells take part in apoptosis regulation.

Objectives and methods:
We investigated whether GPIbα-clustering induces platelet apoptosis through 14-3-3 proteins during cold (4 h 0 °C)-rewarming (1 h 37 °C).

Results:
During cold-rewarming, 14-3-3 proteins associate with GPIbα and dissociate from Bad inducing Bad-dephosphorylation and activation. This initiates pro-apoptosis changes in Bax/Bcl-xL and Bax-translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase-9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N-acetyl-d-glucosamine (GN), which blocks GPIbα-clustering, and by O-sialoglycoprotein endopeptidase, which removes extracellular GPIbα.

Conclusions:
Cold-rewarming triggers apoptosis through a GN-sensitive GPIbα-change indicative of receptor clustering. Attempts to improve platelet transfusion by cold-storage should focus on prevention of the GPIbα-change.
OriginalsprogEngelsk
TidsskriftJournal of Thrombosis and Haemostasis
Vol/bind8
Nummer11
Sider (fra-til)2554-2562
Antal sider9
ISSN1538-7933
DOI
StatusUdgivet - nov. 2010

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