title: Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice.
abstract: When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17(ΔZn/ΔZn) platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage.
authors.affiliation: Translational Medicine Division, Brigham and Women's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: A J Gerard
authors.initials: AJ
authors.lastname: Jansen
authors.forename: Emma C
authors.initials: EC
authors.lastname: Josefsson
authors.forename: Viktoria
authors.initials: V
authors.lastname: Rumjantseva
authors.forename: Qiyong Peter
authors.initials: QP
authors.lastname: Liu
authors.forename: Hervé
authors.initials: H
authors.lastname: Falet
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Cifuni
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hoffmeister
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism / Q000502:physiology; D000072198:ADAM17 Protein; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D001793:Blood Preservation / Q000379:methods; D004789:Enzyme Activation; D006031:Glycosylation; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D045726:Metalloproteases / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000378:metabolism* / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex; D011499:Protein Processing, Post-Translational / Q000502:physiology; D059748:Proteolysis; D012034:Refrigeration / Q000379:methods; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor; D009439:Neuraminidase; D045726:Metalloproteases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse
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