Removal of erythrocyte membrane iron in vivo ameliorates the pathobiology of murine thalassemia

Paul V. Browne, Oded Shalev, Frans A. Kuypers, Carlo Brugnara, Anna Solovey, Narla Mohandas, Stanley L. Schrier, Robert P Hebbel

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Abnormal deposits of free iron are found on the cytoplasmic surface of red blood cell (RBC) membranes in β-thalassemia. To test the hypothesis that this is of importance to RBC pathobiology, we administered the iron chelator deferiprone (L1) intraperitoneally to β-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.

Original languageEnglish (US)
Pages (from-to)1459-1464
Number of pages6
JournalJournal of Clinical Investigation
Volume100
Issue number6
DOIs
StatePublished - Sep 15 1997

Keywords

  • Chelation
  • Iron
  • Membrane
  • Red blood cell
  • Thalassemia

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