title: Glycosylation restores survival of chilled blood platelets.
abstract: Cooling of blood platelets clusters the von Willebrand factor receptor complex. Macrophage alphaMbeta2 integrins bind to the GPIbalpha subunit of the clustered complex, resulting in rapid clearance of transfused, cooled platelets. This precludes refrigeration of platelets for transfusion, but the current practice of room temperature storage has major drawbacks. We document that alphaMbeta2 is a lectin that recognizes exposed beta-N-acetylglucosamine residues of N-linked glycans on GPIbalpha. Enzymatic galactosylation of chilled platelets blocks alphaMbeta2 recognition, prolonging the circulation of functional cooled platelets. Platelet-associated galactosyltransferase produces efficient galactosylation when uridine diphosphate-galactose is added, affording a potentially simple method for storing platelets in the cold.
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. khoffmeister@rics.bwh.harvard.edu
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hoffmeister
authors.forename: Emma C
authors.initials: EC
authors.lastname: Josefsson
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Isaac
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Stossel
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D001793:Blood Preservation; D002236:Carbohydrate Conformation; D002460:Cell Line; D002470:Cell Survival; D003080:Cold Temperature; D005260:Female; D005690:Galactose / Q000378:metabolism*; D005700:Galactosyltransferases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009005:Monosaccharides / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D017713:Platelet Transfusion; D012034:Refrigeration; D014531:Uridine Diphosphate Galactose / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D037102:Lectins; D008024:Ligands; D016177:Macrophage-1 Antigen; D009005:Monosaccharides; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C032193:glycoprotein receptor GPIb-IX; D014841:von Willebrand Factor; D014531:Uridine Diphosphate Galactose; D005700:Galactosyltransferases; D000117:Acetylglucosamine; D005690:Galactose