title: Transferrin therapy ameliorates disease in beta-thalassemic mice.
abstract: Individuals with beta-thalassemia develop progressive systemic iron overload, resulting in high morbidity and mortality. These complications are caused by labile plasma iron, which is taken up by parenchymal cells in a dysregulated manner; in contrast, erythropoiesis depends on transferrin-bound iron uptake via the transferrin receptor. We hypothesized that the ineffective erythropoiesis and anemia observed in beta-thalassemia might be ameliorated by increasing the amount of circulating transferrin. We tested the ability of transferrin injections to modulate iron metabolism and erythropoiesis in Hbb(th1/th1) mice, an experimental model of beta-thalassemia. Injected transferrin reversed or markedly improved the thalassemia phenotype in these mice. Specifically, transferrin injections normalized labile plasma iron concentrations, increased hepcidin expression, normalized red blood cell survival and increased hemoglobin production; this treatment concomitantly decreased reticulocytosis, erythropoietin abundance and splenomegaly. These results indicate that transferrin is a limiting factor contributing to anemia in these mice and suggest that transferrin therapy might be beneficial in human beta-thalassemia.
authors.affiliation: Erythropoiesis Laboratory, Lindsley F Kimball Research Institute, New York Blood Center, New York, New York, USA.
authors.forename: Huihui
authors.initials: H
authors.lastname: Li
authors.forename: Anne C
authors.initials: AC
authors.lastname: Rybicki
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Suzuka
authors.forename: Leni
authors.initials: L
authors.lastname: von Bonsdorff
authors.forename: William
authors.initials: W
authors.lastname: Breuer
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hall
authors.forename: Z Ioav
authors.initials: ZI
authors.lastname: Cabantchik
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
authors.forename: Mary E
authors.initials: ME
authors.lastname: Fabry
authors.forename: Yelena Z
authors.initials: YZ
authors.lastname: Ginzburg
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000097:blood; D006411:Hematopoiesis, Extramedullary; D051379:Mice; D013163:Splenomegaly / Q000188:drug therapy; D014168:Transferrin / Q000008:administration & dosage / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D014168:Transferrin; D004921:Erythropoietin