ROLE OF HEMICHROME BINDING TO ERYTHROCYTE-MEMBRANE IN THE GENERATION OF BAND-3 ALTERATIONS IN BETA-THALASSEMIA-INTERMEDIA ERYTHROCYTES
ROLE OF HEMICHROME BINDING TO ERYTHROCYTE-MEMBRANE IN THE GENERATION OF BAND-3 ALTERATIONS IN BETA-THALASSEMIA-INTERMEDIA ERYTHROCYTES
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DOI：
10.1182/blood.v86.5.2014.bloodjournal8652014
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发表时间：
1995-09-01
期刊：
影响因子：
20.3
通讯作者：
TURRINI, F
中科院分区：
文献类型：
--
作者：
MANNU, F;ARESE, P;TURRINI, F
从60例相似的患者中随机选择9例脾切除、血清学代偿良好的-地中海贫血中间患者进行研究。用非变性洗涤剂C(12)E(8)溶解的膜蛋白在Sepharose CL-6B （Pharmacia Fine Chemicals, Uppsala, Sweden）上进行凝胶过滤。分离并分析了分子量大于4000 - kd的团聚体。4例患者的膜结合半色体和igg数量显著增加。在这些患者中，带3发生氧化修饰，如聚集和巯基减少。其他5例患者有少量的膜结合半色体和较少的3带修饰。同样的带-3修饰可以通过用人工生成的血红素或用高血红素组的地中海贫血红细胞制备的溶血液挑战正常膜来复制。将还原性谷胱甘肽添加到挑战膜上不会阻碍半色素结合，但会阻止能带3的氧化修饰和Ig与高分子量能带3聚集体的结合。血红蛋白与3带结合、血红蛋白介导的3带胞质结构域氧化、高分子量3带聚集体的产生以及抗3带抗体增强的调理作用是导致地中海贫血中红细胞吞噬清除的可能事件序列。(C) 1995年由美国血液病学会出版。
Nine splenectomized, hematologically well-compensated beta-thalassemia intermedia patients randomly chosen from a pool of 60 similar patients were studied. Membrane proteins solubilized with nondenaturing detergent C(12)E(8) 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 hinder 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 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. (C) 1995 by The American Society of Hematology.