Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice. Blood 2012 Feb 02;119(5):1263-73
Date
11/22/2011Pubmed ID
22101895Pubmed Central ID
PMC3277358DOI
10.1182/blood-2011-05-355628Scopus ID
2-s2.0-84863012533 (requires institutional sign-in at Scopus site) 159 CitationsAbstract
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.
Author List
Jansen AJ, Josefsson EC, Rumjantseva V, Liu QP, Falet H, Bergmeier W, Cifuni SM, Sackstein R, von Andrian UH, Wagner DD, Hartwig JH, Hoffmeister KMAuthors
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinKarin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ADAM ProteinsADAM17 Protein
Animals
Blood Platelets
Blood Preservation
Enzyme Activation
Glycosylation
Humans
Male
Membrane Glycoproteins
Metalloproteases
Mice
Mice, Inbred C57BL
Neuraminidase
Platelet Glycoprotein GPIb-IX Complex
Protein Processing, Post-Translational
Proteolysis
Refrigeration
von Willebrand Factor
