Liu S C, Palek J, Prchal J, Castleberry R P
J Clin Invest. 1981 Sep;68(3):597-605. doi: 10.1172/jci110293.
Hereditary pyropoikilocytosis (HPP) is a hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of erythrocytes. We have investigated the contribution of abnormal membrane skeletal assembly to these abnormal HPP erythrocyte properties. Skeletons prepared from fresh HPP ghosts with Triton X-100 were considerably more fragile than skeletons from control erythrocytes. Spectrin, the major skeleton component, extracted at 0 degrees C from normal erythrocytes, was present primarily as tetramers and high molecular weight complexes. In contrast, spectrin extracted from HPP erythrocytes under identical conditions contained a significant amount of dimers with a concomitant decrease of tetramers. Furthermore, spectrin dimers from HPP erythrocytes differed from normal spectrin dimers in their failure to reassociate into tetramers both in solution and in the membrane. Presumptive HPP carriers (asymptomatic mothers of the two patients) exhibited a mild but reproducible increase of spectrin dimers in 0 degrees C extracts and a defective reassociation of spectrin dimers of tetramers both in solution and in the membrane. We conclude that in HPP, self-association of spectrin dimers into tetramers is defective, which accounts for the instability of membrane skeletons.
遗传性热异形红细胞增多症（HPP）是一种溶血性贫血，其特征为小红细胞症、异形红细胞症以及红细胞异常的热敏感性。我们研究了异常的膜骨架组装对这些异常的HPP红细胞特性的影响。用Triton X - 100从新鲜的HPP血影制备的骨架比对照红细胞的骨架脆弱得多。从正常红细胞在0℃提取的主要骨架成分血影蛋白，主要以四聚体和高分子量复合物的形式存在。相比之下，在相同条件下从HPP红细胞中提取的血影蛋白含有大量二聚体，同时四聚体减少。此外，HPP红细胞的血影蛋白二聚体与正常血影蛋白二聚体不同，它们在溶液和膜中都不能重新缔合成四聚体。推定的HPP携带者（两名患者无症状的母亲）在0℃提取物中血影蛋白二聚体有轻度但可重复的增加，并且血影蛋白二聚体在溶液和膜中重新缔合成四聚体均存在缺陷。我们得出结论，在HPP中，血影蛋白二聚体自缔合成四聚体存在缺陷，这导致了膜骨架的不稳定。
