title: Removal of erythrocyte membrane iron in vivo ameliorates the pathobiology of murine thalassemia.
abstract: Abnormal deposits of free iron are found on the cytoplasmic surface of red blood cell (RBC) membranes in beta-thalassemia. To test the hypothesis that this is of importance to RBC pathobiology, we administered the iron chelator deferiprone (L1) intraperitoneally to beta-thalassemic mice for 4 wk and then studied RBC survival and membrane characteristics. L1 therapy decreased membrane free iron by 50% (P = 0.04) and concomitantly improved oxidation of membrane proteins (P = 0.007), the proportion of RBC gilded with immunoglobulin (P = 0.001), RBC potassium content (P < 0.001), and mean corpuscular volume (P < 0.001). Osmotic gradient ektacytometry confirmed a trend toward improvement of RBC hydration status. As determined by clearance of RBC biotinylated in vivo, RBC survival also was significantly improved in L1-treated mice compared with controls (P = 0.007). Thus, in vivo therapy with L1 removes pathologic free iron deposits from RBC membranes in murine thalassemia, and causes improvement in membrane function and RBC survival. This result provides in vivo confirmation that abnormal membrane free iron deposits contribute to the pathobiology of thalassemic RBC.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Browne
authors.forename: O
authors.initials: O
authors.lastname: Shalev
authors.forename: F A
authors.initials: FA
authors.lastname: Kuypers
authors.forename: C
authors.initials: C
authors.lastname: Brugnara
authors.forename: A
authors.initials: A
authors.lastname: Solovey
authors.forename: N
authors.initials: N
authors.lastname: Mohandas
authors.forename: S L
authors.initials: SL
authors.lastname: Schrier
authors.forename: R P
authors.initials: RP
authors.lastname: Hebbel
mesh_terms: D000818:Animals; D002470:Cell Survival; D000077543:Deferiprone; D004910:Erythrocyte Membrane / Q000737:chemistry* / Q000276:immunology; D005914:Globins; D007501:Iron / Q000502:physiology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011728:Pyridones / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013789:Thalassemia / Q000209:etiology*
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D011947:Receptors, Antigen, B-Cell; D000077543:Deferiprone; D005914:Globins; D007501:Iron