Role of sialic acid for platelet life span: exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes.
Although surface sialic acid is considered a key determinant for the survival of circulating blood cells and glycoproteins, its role in platelet circulation lifetime is not fully clarified. We show that thrombocytopenia in mice deficient in the St3gal4 sialyltransferase gene (St3Gal-IV(-/-) mice) is caused by the recognition of terminal galactose residues exposed on the platelet surface in the absence of sialylation. This results in accelerated platelet clearance by asialoglycoprotein receptor-expressing scavenger cells, a mechanism that was recently shown to induce thrombocytopenia during Streptococcus pneumoniae sepsis. We now identify platelet GPIbalpha as a major counterreceptor on ST3Gal-IV(-/-) platelets for asialoglycoprotein receptors. Moreover, we report data that establish the importance of sialylation of the von Willebrand factor in its function.
Sørensen
Anne Louise
AL
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Rumjantseva
Viktoria
V
Nayeb-Hashemi
Sara
S
Clausen
Henrik
H
Hartwig
John H
JH
Wandall
Hans H
HH
Hoffmeister
Karin M
KM
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000235:genetics / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005690:Galactose / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology*; D012799:Sialyltransferases / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D037263:Asialoglycoprotein Receptor; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D005690:Galactose; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase