Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts

Eelo Gitz, Cornelis A. Koekman, Dave J. van den Heuvel, Hans Deckmyn, Jan Willem N. Akkerman, Hans C. Gerritsen, Rolf T. Urbanus: Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts. In: Haematologica, vol. 97, no. 12, pp. 1873-1881, 2012, (cited By (since 1996) 1).

Abstract

Background Storing 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 Methods We examined the change in glycoprotein Ibα distribution using Förster resonance energy transfer by time-gated fluorescence lifetime imaging microscopy. Results Cold storage induced deglycosylation of glycoprotein Ibα ectodomain, exposing N-acetyl-D-glucosamine 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. Conclusions We 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. © 2012 Ferrata Storti Foundation.

BibTeX (Download)

@article{Gitz20121873,
title = {Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts},
author = {Eelo Gitz and Cornelis A. Koekman and Dave J. van den Heuvel and Hans Deckmyn and Jan Willem N. Akkerman and Hans C. Gerritsen and Rolf T. Urbanus},
url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84869885949&partnerID=40&md5=446f25fb0e7209b3093c1006feeb7767},
year  = {2012},
date = {2012-01-01},
journal = {Haematologica},
volume = {97},
number = {12},
pages = {1873-1881},
abstract = {Background Storing 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 Methods We examined the change in glycoprotein Ibα distribution using Förster resonance energy transfer by time-gated fluorescence lifetime imaging microscopy. Results Cold storage induced deglycosylation of glycoprotein Ibα ectodomain, exposing N-acetyl-D-glucosamine 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. Conclusions We 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. © 2012 Ferrata Storti Foundation.},
note = {cited By (since 1996) 1},
keywords = {},
pubstate = {published},
tppubtype = {article}
}