title: A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation.
abstract: We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Jones
authors.forename: Jonas
authors.initials: J
authors.lastname: Denecke
authors.forename: Ronald
authors.initials: R
authors.lastname: Sträter
authors.forename: Torsten
authors.initials: T
authors.lastname: Stölting
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schunicht
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zeuschner
authors.forename: Judith
authors.initials: J
authors.lastname: Klumperman
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Lefeber
authors.forename: Oliver
authors.initials: O
authors.lastname: Spelten
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.forename: Sørge
authors.initials: S
authors.lastname: Kelm
authors.forename: Karen
authors.initials: K
authors.lastname: Strenge
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lühn
authors.forename: Dorothea
authors.initials: D
authors.lastname: Stahl
authors.forename: Luca
authors.initials: L
authors.lastname: Gentile
authors.forename: Thomas
authors.initials: T
authors.lastname: Schreiter
authors.forename: Philip
authors.initials: P
authors.lastname: Hilgard
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.forename: Thorsten
authors.initials: T
authors.lastname: Marquardt
authors.forename: Martin K
authors.initials: MK
authors.lastname: Wild
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002648:Child; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009503:Neutropenia / Q000150:complications / Q000473:pathology; D033704:Nucleotide Transport Proteins / Q000235:genetics; D009844:Oligosaccharides / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013921:Thrombocytopenia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
chemical_list: D037263:Asialoglycoprotein Receptor; D016209:Interleukin-8; D033704:Nucleotide Transport Proteins; D009844:Oligosaccharides; C491081:SLC35A1 protein, human; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D019158:N-Acetylneuraminic Acid