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Dual roles for hepatic lectin receptors in the clearance of chilled platelets

Nature Medicine volume 15, pages 1273–1280 (2009)Cite this article

Abstract

Rapid chilling causes glycoprotein-Ib (GPIb) receptors to cluster on blood platelets. Hepatic macrophage β2 integrin binding to β-N-acetylglucosamine (β-GlcNAc) residues in the clusters leads to rapid clearance of acutely chilled platelets after transfusion. Although capping the β-GlcNAc moieties by galactosylation prevents clearance of short-term–cooled platelets, this strategy is ineffective after prolonged refrigeration. We report here that prolonged refrigeration increased the density and concentration of exposed galactose residues on platelets such that hepatocytes, through Ashwell-Morell receptor binding, become increasingly involved in platelet removal. Macrophages rapidly removed a large fraction of transfused platelets independent of their storage conditions. With prolonged platelet chilling, hepatocyte-dependent clearance further diminishes platelet recovery and survival after transfusion. Inhibition of chilled platelet clearance by both β2 integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold.

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Figure 1: Hepatocytes clear long-term refrigerated platelets.
Figure 2: HepG2 cells ingest long-term–refrigerated human platelets in vitro.
Figure 3: The Ashwell-Morell receptor mediates hepatic recognition and clearance of long-term-refrigerated platelets.
Figure 4: Asialoglycoproteins on long-term–refrigerated human platelets are targets for the Ashwell-Morell receptor on HepG2 cells.
Figure 5: The extracellular domain of GPIb-α is required for recognition of platelets by the Ashwell-Morell receptor.

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Acknowledgements

We thank S. Nayeb-Hashemi for excellent technical assistance, H. Clausen for helpful discussions and F. Maignen for statistical expertise. This work was supported by US National Institutes of Health grant PO1 HL056949 (to J.H.H. and K.M.H.) and grant HL089224 (to K.M.H.); The Pew Scholars Award to K.M.H.; PO1HL57345 (to J.D.M.); Howard Hughes Medical Institute to J.D.M.; and The Swedish Medical Research Council, Göteborg University Jubileums stipend to V.R. and K.M.H. V.R. and H.H.W. received sponsored research support form ZymeQuest, Inc. We obtained macros for K-function analysis from J. Hancock at the Institute for Molecular Bioscience, University of Queensland.

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Author notes

  1. Emma C Josefsson

    Present address: Current address: Walter & Eliza Hall Institute of Medical Research, Molecular Medicine, Parkville, Victoria, Australia.,

Authors and Affiliations

  1. Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Viktoria Rumjantseva, Hans H Wandall, Emma C Josefsson, Anne Louise Sørensen, John H Hartwig & Karin M Hoffmeister

  2. Department of Clinical Chemistry and Transfusion Medicine, Institute of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

    Viktoria Rumjantseva & Göran Larson

  3. The Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA

    Prabhjit K Grewal & Jamey D Marth

  4. Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark

    Anne Louise Sørensen

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Contributions

V.R. wrote the manuscript, planned and performed experiments, data analysis and presentation of all figures; P.K.G. provided Asgr-knockout mice and performed experiments; H.H.W. designed research; E.C.J. performed and analyzed experiments; A.L.S. designed research; G.L. designed research; J.D.M. provided Asgr-knockout mice, laboratory space and equipment; J.H.H. wrote the manuscript and performed experiments; K.M.H. designed research, wrote the manuscript and performed experiments.

Corresponding author

Correspondence to Karin M Hoffmeister.

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Competing interests

H.H.W. and K.M.H. are consultants for ZymeQuest. H.H.W. has stock options in ZymeQuest. H.H.W., K.M.H. and V.R. received sponsored research support form ZymeQuest.

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Rumjantseva, V., Grewal, P., Wandall, H. et al. Dual roles for hepatic lectin receptors in the clearance of chilled platelets. Nat Med 15, 1273–1280 (2009). https://doi.org/10.1038/nm.2030

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