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Platelet apoptosis by cold‐induced glycoprotein Ibα clustering
Author(s) -
VAN DER WAL D. E.,
DU V. X.,
LO K. S. L.,
RASMUSSEN J. T.,
VERHOEF S.,
AKKERMAN J. W. N.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.04043.x
Subject(s) - glycoprotein ib , microbiology and biotechnology , phosphatidylserine , platelet , apoptosis , cytochrome c , chemistry , platelet activation , biology , biochemistry , immunology , phospholipid , membrane
Summary. Background: Cold‐storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα‐distribution indicative of receptor clustering and initiates thromboxane A 2 ‐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‐x L 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.