The unusual pathobiology of hemoglobin constant spring red blood cells.
The unusual pathobiology of hemoglobin constant spring red blood cells.
复制标题
DOI：
10.1182/blood.v89.5.1762
复制
发表时间：
1997-03
期刊：
影响因子：
20.3
通讯作者：
S. L. Schrier;A. Bunyaratvej;A. Khuhapinant;S. Fucharoen;M. Aljurf;LM Snyder;C. Keifer;Lisa Ma;Narla Mohandas
中科院分区：
文献类型：
--
作者：
S. L. Schrier;A. Bunyaratvej;A. Khuhapinant;S. Fucharoen;M. Aljurf;LM Snyder;C. Keifer;Lisa Ma;Narla Mohandas
血红蛋白恒定弹簧（HbCS）是最常见的非缺失型α-地中海贫血突变，是东南亚HbH样疾病的重要原因。HbCS变体具有几乎正常的平均细胞体积（MCV），并且与其他α-地中海贫血变体相比，贫血更严重。我们探索了HbCS红细胞（RBC）的病理生物学，因为HbCS的MCV“正常化”效应和更严重贫血的根本原因尚未完全解释。相对于缺失型α-地中海贫血变体，含HbCS的RBC明显过度水合，并且体积调节和细胞水合的紊乱发生在红细胞成熟的早期，并且在网织红细胞阶段完全表达。此外，当与HbH和α-地中海贫血-1性状RBC相比时，含HbCS的RBC的膜刚性和膜机械稳定性增加。在寻找这些细胞改变的潜在原因时，我们分析了来自HbCS和缺失性α-地中海贫血变体的膜，并发现除了氧化的β-珠蛋白链之外，氧化的α-cs-珠蛋白链也与含有HbCS的RBC中的膜及其骨架相关。我们提出，HbCS变体的膜病理是由膜结合的氧化α CS-和β-珠蛋白链诱导的有害作用的组合引起的。由α cs链诱导的膜改变更类似于由β A-珠蛋白链诱导的膜改变，而不是由在β-地中海贫血中积累的α A-珠蛋白链诱导的膜改变。因此，每个珠蛋白链，α cs，α A，β A，似乎产生其自身形式的膜扰动。
Hemoglobin Constant Spring (HbCS) is the most common nondeletional alpha-thalassemic mutation and is an important cause of HbH-like disease in Southeast Asia. HbCS variants have an almost normal mean cell volume (MCV) and the anemia is more severe when compared with other alpha-thalassemic variants. We explored the pathobiology of HbCS red blood cells (RBCs) because the underlying cause(s) of this MCV "normalizing" effect of HbCS and the more severe anemia are not fully explained. HbCS containing RBCs are distinctly overhydrated relative to deletional alpha-thalassemia variants, and the derangement of volume regulation and cell hydration occurs early in erythroid maturation and is fully expressed at the reticulocyte stage. Furthermore, the membrane rigidity and membrane mechanical stability of HbCS containing RBCs is increased when compared with HbH and alpha-thalassemia-1 trait RBCs. In seeking the cause(s) underlying these cellular alterations we analyzed membranes from HbCS and deletional alpha-thalassemic variants and found that in addition to oxidized beta-globin chains, oxidized alpha cs-globin chains are also associated with the membranes and their skeletons in HbCS containing RBCs. We propose that the membrane pathology of HbCS variants is caused by combination of the deleterious effects induced by membrane-bound oxidized alpha cs- and beta-globin chains. The membrane alterations induced by alpha cs chains are more akin to those induced by beta A-globin chains than those induced by the alpha A-globin chains that accumulate in the beta-thalassemias. Thus, each globin chain, alpha cs, alpha A, beta A, appears to produce its own form of membrane perturbation.