Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 12 September 2003:
Vol. 301. no. 5639, pp. 1531 - 1534
DOI: 10.1126/science.1085322

Reports

Glycosylation Restores Survival of Chilled Blood Platelets

Karin M. Hoffmeister,1* Emma C. Josefsson,1,2 Natasha A. Isaac,1 Henrik Clausen,3,4 John H. Hartwig,1 Thomas P. Stossel1

Cooling of blood platelets clusters the von Willebrand factor receptor complex. Macrophage {alpha}Mß2 integrins bind to the GPIb{alpha} subunit of the clustered complex, resulting in rapid clearance of transfused, cooled platelets. This precludes refrigeration of platelets for transfusion, but the current practice of room temperature storage has major drawbacks. We document that {alpha}Mß2 is a lectin that recognizes exposed ß-N-acetylglucosamine residues of N-linked glycans on GPIb{alpha}. Enzymatic galactosylation of chilled platelets blocks {alpha}Mß2 recognition, prolonging the circulation of functional cooled platelets. Platelet-associated galactosyltransferase produces efficient galactosylation when uridine diphosphate–galactose is added, affording a potentially simple method for storing platelets in the cold.

1 Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
3 Department of Oral Diagnostics, University of Copenhagen, School of Dentistry, Copenhagen, Denmark.
4 Zymequest, Inc., Beverly, MA 01915, USA.

* To whom correspondence should be addressed. E-mail: khoffmeister{at}rics.bwh.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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.
A. L. Sorensen, V. Rumjantseva, S. Nayeb-Hashemi, H. Clausen, J. H. Hartwig, H. H. Wandall, and K. M. Hoffmeister (2009)
Blood 114, 1645-1654
   Abstract »    Full Text »    PDF »
Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-Associated N-Acetylglucosamine Glycan Antigens.
T. Satomaa, A. Heiskanen, I. Leonardsson, J. Angstrom, A. Olonen, M. Blomqvist, N. Salovuori, C. Haglund, S. Teneberg, J. Natunen, et al. (2009)
Cancer Res. 69, 5811-5819
   Abstract »    Full Text »    PDF »
An N-Glycosylation Site on the{beta}-Propeller Domain of the Integrin {alpha}5 Subunit Plays Key Roles in Both Its Function and Site-specific Modification by{beta}1,4-N-Acetylglucosaminyltransferase III.
Y. Sato, T. Isaji, M. Tajiri, S. Yoshida-Yamamoto, T. Yoshinaka, T. Somehara, T. Fukuda, Y. Wada, and J. Gu (2009)
J. Biol. Chem. 284, 11873-11881
   Abstract »    Full Text »    PDF »
Thrombocytopenia and Platelet Abnormalities in High-Density Lipoprotein Receptor-Deficient Mice.
V. S. Dole, J. Matuskova, E. Vasile, A. Yesilaltay, W. Bergmeier, M. Bernimoulin, D. D. Wagner, and M. Krieger (2008)
Arterioscler Thromb Vasc Biol 28, 1111-1116
   Abstract »    Full Text »    PDF »
Platelets come back in from the cold.
M. Lozano (2008)
Blood 111, 2951
   Full Text »    PDF »
Galactosylation does not prevent the rapid clearance of long-term, 4{degrees}C-stored platelets.
H. H. Wandall, K. M. Hoffmeister, A. L. Sorensen, V. Rumjantseva, H. Clausen, J. H. Hartwig, and S. J. Slichter (2008)
Blood 111, 3249-3256
   Abstract »    Full Text »    PDF »
Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance.
M. Othman, A. Labelle, I. Mazzetti, H. S. Elbatarny, and D. Lillicrap (2007)
Blood 109, 2832-2839
   Abstract »    Full Text »    PDF »
Transfusion medicine.
T. R. Klumpp and D. L. Siegel (2007)
ASH Self-Assessment Program 2007, 408-443
   Full Text »    PDF »
In Vivo Studies of Autologous Platelets Stored at Room Temperature (22{degrees}C), 4{degrees}C, and 4{degrees}C with Galactosylation..
S. J. Slichter, H. H. Wandall, and K. M. Hoffmeister (2006)
Blood (ASH Annual Meeting Abstracts) 108, 580
   Abstract »    PDF »
N-Glycosylation of the beta-Propeller Domain of the Integrin {alpha}5 Subunit Is Essential for {alpha}5beta1 Heterodimerization, Expression on the Cell Surface, and Its Biological Function.
T. Isaji, Y. Sato, Y. Zhao, E. Miyoshi, Y. Wada, N. Taniguchi, and J. Gu (2006)
J. Biol. Chem. 281, 33258-33267
   Abstract »    Full Text »    PDF »
Activation-independent, antibody-mediated removal of GPVI from circulating human platelets: development of a novel NOD/SCID mouse model to evaluate the in vivo effectiveness of anti-human platelet agents.
B. Boylan, M. C. Berndt, M. L. Kahn, and P. J. Newman (2006)
Blood 108, 908-914
   Abstract »    Full Text »    PDF »
The structure of the GPIb-filamin A complex.
F. Nakamura, R. Pudas, O. Heikkinen, P. Permi, I. Kilpelainen, A. D. Munday, J. H. Hartwig, T. P. Stossel, and J. Ylanne (2006)
Blood 107, 1925-1932
   Abstract »    Full Text »    PDF »
Platelets: Testing, Dosing and the Storage Lesion--Recent Advances.
R. M. Kaufman (2006)
Hematology 2006, 492-496
   Abstract »    Full Text »    PDF »
The Macrophage {alpha}M{beta}2 Integrin {alpha}M Lectin Domain Mediates the Phagocytosis of Chilled Platelets.
E. C. Josefsson, H. H. Gebhard, T. P. Stossel, J. H. Hartwig, and K. M. Hoffmeister (2005)
J. Biol. Chem. 280, 18025-18032
   Abstract »    Full Text »    PDF »
Acquired Disorders of Platelet Function.
A. A. Hassan and M. H. Kroll (2005)
Hematology 2005, 403-408
   Abstract »    Full Text »    PDF »
LDL-receptor-related protein regulates {beta}2-integrin-mediated leukocyte adhesion.
P. P. E. M. Spijkers, P. da Costa Martins, E. Westein, C. G. Gahmberg, J. J. Zwaginga, and P. J. Lenting (2005)
Blood 105, 170-177
   Abstract »    Full Text »    PDF »
An Externally Active Endogenous Platelet Galactosyl Trasferase (Gal-T)..
K. M. Hoffmeister, H. H. Wandall, V. Sankaranarayanan, H. Clausen, T. P. Stossel, and J. H. Hartwig (2004)
Blood (ASH Annual Meeting Abstracts) 104, 3525
   Abstract »
Glycosylation engineering enhances stem cell homing.
A. Varki (2004)
Blood 104, 3005
   Full Text »    PDF »
The integrin {alpha}M{beta}2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization.
A. Hidalgo, A. J. Peired, L. A. Weiss, Y. Katayama, and P. S. Frenette (2004)
Blood 104, 993-1001
   Abstract »    Full Text »    PDF »
Basic Science Breakthrough in Platelet Transfusion.
(2003)
Journal Watch (General) 2003, 3
   Full Text »
Targeting Platelet-Leukocyte Interactions: Identification of the Integrin Mac-1 Binding Site for the Platelet Counter Receptor Glycoprotein Ib{alpha}.
R. Ehlers, V. Ustinov, Z. Chen, X. Zhang, R. Rao, F. W. Luscinskas, J. Lopez, E. Plow, and D. I. Simon (2003)
J. Exp. Med. 198, 1077-1088
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)