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Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice

Oldenborg, P. A.
Gresham, H. D.
Chen, Yongmei
Lindberg, F. P.
Published in Blood. 2002, vol. 99, no. 10, p. 3500-3504
Abstract The glycoprotein CD47 (integrin-associated protein, IAP) is present on the surface of virtually all cells, including red blood cells (RBCs). CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein alpha (SIRPalpha). In this manner mild reactivity of wild-type RBCs with macrophage phagocytic receptors is tolerated, whereas otherwise identical CD47-deficient RBCs are rapidly eliminated. We show here that virtually all CD47-deficient nonobese diabetic (NOD) mice spontaneously develop severe lethal autoimmune hemolytic anemia (AIHA) at 180 to 280 days of age, whereas none of the control CD47(+) NOD mice develop lethal AIHA at least during the first year of life. This phenotype is at least partially due to a markedly increased rate of elimination of opsonized CD47(-/-) compared to CD47(+) RBCs. Similarly, CD47(-/-)C57BL/6 mice were much more sensitive than their wild-type counterparts to experimental passive AIHA induced by anti-RBC monoclonal antibodies. Thus, CD47-SIRPalpha signaling can have a profound influence on the severity of AIHA, making manipulation of this signaling pathway a theoretically appealing avenue in the treatment of the disease.
Keywords Anemia, Hemolytic, Autoimmune/diagnosis/ etiology/mortalityAnimalsAntigens, CD/genetics/ physiologyAntigens, CD47Carrier Proteins/genetics/ physiologyDisease ProgressionErythrocyte TransfusionErythrocytes/chemistry/immunologyFemaleKineticsMaleMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutModels, BiologicalSurvival Rate
PMID: 11986200
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OLDENBORG, P. A. et al. Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice. In: Blood, 2002, vol. 99, n° 10, p. 3500-3504. doi: 10.1182/blood.v99.10.3500

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Deposited on : 2010-08-27

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