| First Author | Oldenborg PA | Year | 2002 |
| Journal | Blood | Volume | 99 |
| Issue | 10 | Pages | 3500-4 |
| PubMed ID | 11986200 | Mgi Jnum | J:76580 |
| Mgi Id | MGI:2179694 | Doi | 10.1182/blood.v99.10.3500 |
| Citation | Oldenborg PA, et al. (2002) Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice. Blood 99(10):3500-4 |
| abstractText | 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. |
