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Science 16 June 2000:
Vol. 288. no. 5473, pp. 2051 - 2054
DOI: 10.1126/science.288.5473.2051
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Reports

Role of CD47 as a Marker of Self on Red Blood Cells

Per-Arne Oldenborg, 1 Alex Zheleznyak, 1 Yi-Fu Fang, 1 Carl F. Lagenaur, 2 Hattie D. Gresham, 3 Frederik P. Lindberg 1*

The immune system recognizes invaders as foreign because they express determinants that are absent on host cells or because they lack "markers of self" that are normally present. Here we show that CD47 (integrin-associated protein) functions as a marker of self on murine red blood cells. Red blood cells that lacked CD47 were rapidly cleared from the bloodstream by splenic red pulp macrophages. CD47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein alpha (SIRPalpha ). Thus, macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign. CD47-SIRPalpha may represent a potential pathway for the control of hemolytic anemia.

1 Division of Infectious Diseases, Department of Internal Medicine, Campus Box 8051, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
2 Department of Neurobiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
3 Research Service, Albuquerque VA Medical Center, Albuquerque, NM 87108, USA.
*   To whom correspondence should be addressed. E-mail: lindberg{at}id.wustl.edu

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   Abstract »    Full Text »    PDF »
Negative Regulation of Platelet Clearance and of the Macrophage Phagocytic Response by the Transmembrane Glycoprotein SHPS-1.
T. Yamao, T. Noguchi, O. Takeuchi, U. Nishiyama, H. Morita, T. Hagiwara, H. Akahori, T. Kato, K. Inagaki, H. Okazawa, et al. (2002)
J. Biol. Chem. 277, 39833-39839
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Mechanisms of CD47-induced caspase-independent cell death in normal and leukemic cells: link between phosphatidylserine exposure and cytoskeleton organization.
V. Mateo, E. J. Brown, G. Biron, M. Rubio, A. Fischer, F. L. Deist, and M. Sarfati (2002)
Blood 100, 2882-2890
   Abstract »    Full Text »    PDF »
Absence of CD47 in protein 4.2-deficient hereditary spherocytosis in man: an interaction between the Rh complex and the band 3 complex.
L. J. Bruce, S. Ghosh, M. J. King, D. M. Layton, W. J. Mawby, G. W. Stewart, P.-A. Oldenborg, J. Delaunay, and M. J. A. Tanner (2002)
Blood 100, 1878-1885
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Signal-Regulatory Protein {alpha}-CD47 Interactions Are Required for the Transmigration of Monocytes Across Cerebral Endothelium.
H. E. de Vries, J. J. A. Hendriks, H. Honing, C. R. de Lavalette, S. M. A. van der Pol, E. Hooijberg, C. D. Dijkstra, and T. K. van den Berg (2002)
J. Immunol. 168, 5832-5839
   Abstract »    Full Text »    PDF »
Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice.
P.-A. Oldenborg, H. D. Gresham, Y. Chen, S. Izui, and F. P. Lindberg (2002)
Blood 99, 3500-3504
   Abstract »    Full Text »    PDF »
Signal Regulatory Protein (SIRPalpha ), a Cellular Ligand for CD47, Regulates Neutrophil Transmigration.
Y. Liu, H.-J. Buhring, K. Zen, S. L. Burst, F. J. Schnell, I. R. Williams, and C. A. Parkos (2002)
J. Biol. Chem. 277, 10028-10036
   Abstract »    Full Text »    PDF »
Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells.
F. Zhan, J. Hardin, B. Kordsmeier, K. Bumm, M. Zheng, E. Tian, R. Sanderson, Y. Yang, C. Wilson, M. Zangari, et al. (2002)
Blood 99, 1745-1757
   Abstract »    Full Text »    PDF »
Elimination of Porcine Hemopoietic Cells by Macrophages in Mice.
M. Abe, J. Cheng, J. Qi, R. M. Glaser, A. D. Thall, M. Sykes, and Y.-G. Yang (2002)
J. Immunol. 168, 621-628
   Abstract »    Full Text »    PDF »
Red Cell Antigens as Functional Molecules and Obstacles to Transfusion.
G. Garratty, M. J. Telen, and L. D. Petz (2002)
Hematology 2002, 445-462
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The Role of CD47 in Neutrophil Transmigration. INCREASED RATE OF MIGRATION CORRELATES WITH INCREASED CELL SURFACE EXPRESSION OF CD47.
Y. Liu, D. Merlin, S. L. Burst, M. Pochet, J. L. Madara, and C. A. Parkos (2001)
J. Biol. Chem. 276, 40156-40166
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Bidirectional Negative Regulation of Human T and Dendritic Cells by CD47 and Its Cognate Receptor Signal-Regulator Protein-{alpha}: Down-Regulation of IL-12 Responsiveness and Inhibition of Dendritic Cell Activation.
S. Latour, H. Tanaka, C. Demeure, V. Mateo, M. Rubio, E. J. Brown, C. Maliszewski, F. P. Lindberg, A. Oldenborg, A. Ullrich, et al. (2001)
J. Immunol. 167, 2547-2554
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Cd47 (Integrin-Associated Protein) Engagement of Dendritic Cell and Macrophage Counterreceptors Is Required to Prevent the Clearance of Donor Lymphohematopoietic Cells.
B. R. Blazar, F. P. Lindberg, E. Ingulli, A. Panoskaltsis-Mortari, P.-A. Oldenborg, K. Iizuka, W. M. Yokoyama, and P. A. Taylor (2001)
J. Exp. Med. 194, 541-550
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Unavailability of CD147 leads to selective erythrocyte trapping in the spleen.
I. Coste, J.-F. Gauchat, A. Wilson, S. Izui, P. Jeannin, Y. Delneste, H. R. MacDonald, J.-Y. Bonnefoy, and T. Renno (2001)
Blood 97, 3984-3988
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Long-Circulating and Target-Specific Nanoparticles: Theory to Practice.
S. M. Moghimi, A. C. Hunter, and J. C. Murray (2001)
Pharmacol. Rev. 53, 283-318
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Cd47-Signal Regulatory Protein {alpha} (Sirp{alpha}) Regulates Fc{gamma} and Complement Receptor-Mediated Phagocytosis.
P.-A. Oldenborg, H. D. Gresham, and F. P. Lindberg (2001)
J. Exp. Med. 193, 855-862
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CD47, a Ligand for the Macrophage Fusion Receptor, Participates in Macrophage Multinucleation.
X. Han, H. Sterling, Y. Chen, C. Saginario, E. J. Brown, W. A. Frazier, F. P. Lindberg, and A. Vignery (2000)
J. Biol. Chem. 275, 37984-37992
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Normal Ligand Binding and Signaling by CD47 (Integrin-associated Protein) Requires a Long Range Disulfide Bond between the Extracellular and Membrane-spanning Domains.
R. A. Rebres, L. E. Vaz, J. M. Green, and E. J. Brown (2001)
J. Biol. Chem. 276, 34607-34616
   Abstract »    Full Text »    PDF »


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