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BackgroundStoring platelets for transfusion at room temperature increases the risk of microbial infection and decreases platelet functionality, leading to out-date discard rates of up to 20%. Cold storage may be a better alternative, but this treatment leads to rapid platelet clearance after transfusion, initiated by changes in glycoprotein Ibα, the receptor for von Willebrand factor.
Design and MethodsWe examined the change in glycoprotein Ibα distribution using Förster resonance energy transfer by time-gated fluorescence lifetime imaging microscopy.
ResultsCold storage induced deglycosylation of glycoprotein Ibα ectodomain, exposing N-acetyl-Dglucosamine residues, which sequestered with GM1 gangliosides in lipid rafts. Raft-associated glycoprotein Ibα formed clusters upon binding of 14-3-3ζ adaptor proteins to its cytoplasmic tail, a process accompanied by mitochondrial injury and phosphatidyl serine exposure. Cold storage left glycoprotein Ibα surface expression unchanged and although glycoprotein V decreased, the fall did not affect glycoprotein Ibα clustering. Prevention of glycoprotein Ibα clustering by blockade of deglycosylation and 14-3-3ζ translocation increased the survival of cold-stored platelets to above the levels of platelets stored at room temperature without compromising hemostatic functions.
ConclusionsWe conclude that glycoprotein Ibα translocates to lipid rafts upon cold-induced deglycosylation and forms clusters by associating with 14-3-3ζ. Interference with these steps provides a means to enable cold storage of platelet concentrates in the near future.Key words: platelets, cold storage, glycoprotein Ibα, 14-3-3ζ, lipid raft, clustering. Ibα clustering in lipid rafts. Haematologica 2012;97(12):1873-1881. doi:10.3324/haematol.2012 This is an open-access paper.
Citation: Gitz E, Koekman CA, van den Heuvel DJ, Deckmyn H, Akkerman JW, Gerritsen HC and Urbanus RT. Improved platelet survival after cold storage by prevention of glycoprotein
Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts
ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n