Membrane phospholipid asymmetry in human thalassemia
Membrane phospholipid asymmetry in human thalassemia
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DOI：
10.1182/blood.v91.8.3044.3044_3044_3051
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发表时间：
1998-04-15
期刊：
影响因子：
20.3
通讯作者：
Schrier, SL
中科院分区：
文献类型：
--
作者：
Kuypers, FA;Yuan, J;Schrier, SL
红细胞（RBC）脂质双层中的磷脂不对称性在细胞的寿命期间保持良好，磷脂酰丝氨酸（PS）几乎完全位于内层单层中。磷脂不对称性的丧失，以及随后的PS暴露，被认为在红细胞病理学中起重要作用。人地中海贫血中的贫血是由无效的红细胞生成（髓内溶血）和外周血中成人RBC存活减少的组合引起的。地中海贫血红细胞的这种过早破坏可能部分是由于磷脂不对称性的丧失，因为暴露PS的细胞被巨噬细胞识别并清除。此外，PS暴露可在重度中间型β地中海贫血报告存在的高凝状态中发挥作用。我们描述了56例不同遗传背景的α-或β-地中海贫血表型的贫血患者的红细胞PS暴露。使用荧光标记的膜联蛋白V使我们能够确定单个细胞中磷脂不对称性的损失。我们的数据表明，在一些地中海贫血患者中，红细胞亚群循环暴露PS在其外表面。这种细胞的数量在不同的患者之间有很大的差异，从正常对照组中发现的低（小于0.2%）到20%。β-地中海贫血红细胞的荧光显微镜分析表明，外叶上的PS分布在整个膜上或定位在可能与富含膜结合α-珠蛋白链的区域相关的区域。我们推测，这些膜位点，其中铁携带珠蛋白链积累和导致氧化损伤，可能是重要的损失膜脂质组织。总之，我们报告了PS暴露的地中海贫血红细胞亚群的存在，这些亚群最有可能具有生理重要性，因为它们可以提供一个表面，以加强止血，因为这种暴露可能介导这些红细胞从循环中快速清除，从而导致贫血。(C)1998年，美国血液学会。
Phospholipid asymmetry in the red blood cell (RBC) lipid bilayer is well maintained during the life of the cell, with phosphatidylserine (PS) virtually exclusively located in the inner monolayer. Loss of phospholipid asymmetry, and consequently exposure of PS, is thought to play an important role in red cell pathology. The anemia in the human thalassemias is caused by a combination of ineffective erythropoiesis (intramedullary hemolysis) and a decreased survival of adult RBCs in the peripheral blood. This premature destruction of the thalassemic RBC could in part be due to a loss of phospholipid asymmetry, because cells that expose PS are recognized and removed by macrophages. In addition, PS exposure can play a role in the hypercoagulable state reported to exist in severe beta-thalassemia intermedia. We describe PS exposure in RBCs of 56 comparably anemic patients with different genetic backgrounds of the alpha- or beta-thalassemia phenotype. The use of fluorescently labeled annexin V allowed us to determine loss of phospholipid asymmetry in individual cells. Our data indicate that in a number of thalassemic patients, subpopulations of red cells circulate that expose PS on their outer surface. The number of such cells can vary dramatically from patient to patient, from as low as that found in normal controls (less than 0.2%) up to 20%. Analysis by fluorescent microscopy of beta-thalassemic RBCs indicates that PS on the outer leaflet is distributed either over the entire membrane or localized in areas possibly related to regions rich in membrane-bound alpha-globin chains. We hypothesize that these membrane sites in which iron carrying globin chains accumulate and cause oxidative damage, could be important in the loss of membrane lipid organization. In conclusion, we report the presence of PS-exposing subpopulations of thalassemic RBC that are most likely physiologically important, because they could provide a surface for enhancing hemostasis as recently reported, and because such exposure may mediate the rapid removal of these RBCs from the circulation, thereby contributing to the anemia. (C) 1998 by The American Society of Hematology.