Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice.
2002 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 99, no 10, 3500-4 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2002. Vol. 99, no 10, 3500-4 p.
IdentifiersURN: urn:nbn:se:umu:diva-82576PubMedID: 11986200OAI: oai:DiVA.org:umu-82576DiVA: diva2:661922