Mohandas N, Clark M R, Wyatt J L, Garcia J F, Eisenberg P D, Shohet S B
Blood. 1980 May;55(5):757-61.
Hemoglobin switching and macrocytosis were studied in homozygous hemoglobinAA sheep. An abrupt initiation of erythropoietic stress, accompanied by a pulsed elevation of circulating erythropoietin levels, was induced by phlebotomy. Sequential blood samples were separated according to density on Stractan gradients to isolate cells newly entering the circulation from the marrow each day. Analysis of hemoglobin phenotype and cell volume distribution in these young reticulocytes revealed a distinct temporal separation in the appearance of hemoglobin C and increased cell volume. The appearance of macrocytes within 24 hr of erythropoietin elevation suggests that macrocytosis could be the result of the action of erythropoietin during the late stages of erythroid maturation. The 72-hr delay in the appearance of hemoglobin C indicates that commitment to a particular hemoglobin phenotype occurs at an early stage of differentiation and involves immature erythroid stem cells. The results of this study show that these consequences of erythropoietic stress are initiated at two different developmental stages, resulting in the production of macrocytosis and hemoglobin switching.
在纯合血红蛋白 AA 绵羊中研究了血红蛋白转换和大红细胞症。通过放血诱导突然开始的红细胞生成应激，伴随着循环促红细胞生成素水平的脉冲式升高。每天根据密度在 Stractan 梯度上分离连续的血样，以从骨髓中分离新进入循环的细胞。对这些年轻网织红细胞中的血红蛋白表型和细胞体积分布进行分析，发现血红蛋白 C 的出现和细胞体积增加在时间上有明显的分离。促红细胞生成素升高后 24 小时内出现大红细胞表明，大红细胞症可能是促红细胞生成素在红细胞成熟后期作用的结果。血红蛋白 C 出现延迟 72 小时表明，向特定血红蛋白表型的定向分化发生在分化的早期阶段，且涉及未成熟的红细胞干细胞。本研究结果表明，红细胞生成应激的这些后果在两个不同的发育阶段开始，导致大红细胞症和血红蛋白转换的产生。
