Role of hemichrome binding to erythrocyte membrane in the generation of band-3 alterations in β-thalassemia intermedia erythrocytes

F. Mannu, P. Arese, M. D. Cappellini, G. Fiorelli, M. Cappadoro, G. Giribaldi, F. Turrini

Research output: Contribution to journalArticle

Abstract

Nine splenectomized, hematologically well-compensated β-thalassemia intermedia patients randomly chosen from a pool of 60 similar patients were studied. Membrane proteins solubilized with nondenaturing detergent C12E8 were gel filtered on Sepharose CL-6B (Pharmacia Fine Chemicals, Uppsala, Sweden). Fractions containing higher than 4,000-kD molecular-weight aggregates were isolated and analyzed. Four patients had remarkably increased amounts of membrane-bound hemichromes and Igs. In those patients, band 3 underwent oxidative modifications such as aggregation and a decrease in sulfhydryl groups. The other five patients had low amounts of membrane-bound hemichromes and less modifications of band 3. The same band-3 modifications could be reproduced by challenging normal membranes with artificially generated hemichromes or with hemolysates prepared from thalassemic erythrocytes of the high-hemichrome group. Addition of reduced glutathione to the challenged membranes did not binder hemichrome binding, but prevented oxidative modifications of band 3 and Ig binding to high-molecular-weight band-3 aggregates. Hemichrome binding to band 3, hemichrome-mediated oxidation of band-3 cytoplasmic domains, generation of high-molecular-weight band-3 aggregates, and enhanced opsonization by anti-band-3 antibodies is a possible sequence of events leading to phagocytic removal of erythrocytes in thalassemia.

Original languageEnglish
Pages (from-to)2014-2020
Number of pages7
JournalBlood
Volume86
Issue number5
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Hematology

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    Mannu, F., Arese, P., Cappellini, M. D., Fiorelli, G., Cappadoro, M., Giribaldi, G., & Turrini, F. (1995). Role of hemichrome binding to erythrocyte membrane in the generation of band-3 alterations in β-thalassemia intermedia erythrocytes. Blood, 86(5), 2014-2020.