Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice.
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.
Oldenborg
Per-Arne
PA
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, Sweden. per-arne.oldenborg@histocel.umu.se
Gresham
Hattie D
HD
Chen
Yongmei
Y
Izui
Shozo
S
Lindberg
Frederik P
FP
D000744:Anemia, Hemolytic, Autoimmune / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology; D005260:Female; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008954:Models, Biological; D015996:Survival Rate
D015703:Antigens, CD; D051928:CD47 Antigen; D002352:Carrier Proteins; C497895:Cd47 protein, mouse