Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts.
Haematologica
; 97(12): 1873-81, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-22733027
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 ANDMETHODS:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Complexo Glicoproteico GPIb-IX de Plaquetas
/
Microdomínios da Membrana
/
Proteínas 14-3-3
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Gangliosídeo G(M1)
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article