DEFICIENCY OF SKELETAL MEMBRANE-PROTEIN BAND 4.1 IN HOMOZYGOUS HEREDITARY ELLIPTOCYTOSIS - IMPLICATIONS FOR ERYTHROCYTE-MEMBRANE STABILITY
DEFICIENCY OF SKELETAL MEMBRANE-PROTEIN BAND 4.1 IN HOMOZYGOUS HEREDITARY ELLIPTOCYTOSIS - IMPLICATIONS FOR ERYTHROCYTE-MEMBRANE STABILITY
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DOI：
10.1172/jci110275
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发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
SHOHET, SB
中科院分区：
文献类型：
--
作者：
TCHERNIA, G;MOHANDAS, N;SHOHET, SB
本文对3例严重溶血性贫血、红细胞明显碎裂和椭圆形异形红细胞症患者的红细胞进行了膜蛋白组成和机械特性的研究。还研究了患者父母和1名轻微受累和1名正常同胞的红细胞。形态学观察结果表明，严重影响的患者患有纯合子遗传性椭圆形红细胞增多症，因为父母双方和1个受影响最小的兄弟姐妹的红细胞在涂片上显示中度椭圆形红细胞增多症;未受影响的兄弟姐妹的红细胞形态正常。患者红细胞膜蛋白带4.1水平显著降低，父母和假定杂合子同胞红细胞带4.1水平中度降低，这一平行结果表明，细胞的椭圆形与带4.1水平降低有关。进一步的研究表明，纯合子患者红细胞的细胞变形性和膜脆性明显异常。这些变化也与条带4.1水平的降低密切相关，表明该蛋白在维持正常膜稳定性和正常细胞形状中起着重要作用。条带4.1的这种作用可能与其通过与血影蛋白和肌动蛋白的连接而与膜骨架的已知生化连接密切相关。
Erthrocytes from 3 patients with severe hemolytic anemia, marked erythrocyte fragmentation and elliptocytic poikilocytosis were studied in terms of both their membrane protein composition and their mechanical characteristics. Erythrocytes from the patients'' parents and 1 minimally affected and 1 normal sibling were also studied. Morphologic observations implied that the severely affected patients suffered from homozygous hereditary elliptocytosis because erythrocytes of both parents and the 1 minimally affected sibling showed moderate elliptocytosis on smear; those of an unaffected sibling had normal morphology. The parallel findings of markedly reduced levels of band 4.1 in the erythrocyte membrane proteins of the patients and an intermediate reduction in the cells of the parents and the putative heterozygous sibling, suggested that the elliptocytic shape of the cells was related to the reduced levels of band 4.1. Additional studies showed marked abnormalities in cellular deformability and membrane fragility in the erythrocytes from the homozygous patients. These changes were also closely proportional to the reduced levels of band 4.1, suggesting a central role for this protein in the maintenance of normal membrane stability and normal cell shape. This role for band 4.1 is probably intimately related to its known biochemical connection to the membrane skeleton through its linkage with spectrin and actin.