Determination of the hemoglobin F program in human progenitor-derived erythroid cells.
Determination of the hemoglobin F program in human progenitor-derived erythroid cells.
复制标题
人祖源性红细胞中血红蛋白 F 程序的测定。
DOI：
10.1172/jci111837
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Nathan,DG
中科院分区：
文献类型：
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作者：
Friedman,AD;Linch,DC;Miller,B;Lipton,JM;Javid,J;Nathan,DG
正常人和猿类红系祖细胞分化产生的红系细胞以及非缺失性血红蛋白病患者的外周血红系爆发形成单位 (BFU-E) 的成人和胎儿血红蛋白 (HbF) 绝对含量已通过灵敏的放射性配体免疫测定法进行了测量。 HbF 含量在 0.13 至 2.96 pg/细胞之间变化，占总血红蛋白的 0.7% 至 19.6%，平均值为 7.0%。 HbF 的绝对含量在骨髓红细胞集落形成单位、骨髓或血液 BFU-E 或混合集落形成单位的血红蛋白化良好的后代中无法区分。术语 HbF 程序是指在体外源自这些祖细胞的红细胞中产生胎儿血红蛋白 (HbF) 的固有能力。通过相同的放射性配体免疫测定法测定的骨髓成红细胞的 HbF 含量与外周血中发现的相似，这表明伽马链产生的关闭发生在红细胞集落形成单位成熟阶段之后。含促红细胞生成素粗制品浓度的增加会诱导更多数量的红细胞集落，其尺寸也更大，但 HbF 程序不受影响。与人类祖细胞群中血红蛋白的积累相反，猿猴祖细胞群产生了更多的 HbF，并且 HbF 的量受到祖细胞成熟度的强烈影响。对来自非缺失性血红蛋白病患者及其父母的外周血 BFU-E 培养物的成红细胞的 HbF 含量测定表明，此类患者祖细胞中的 HbF 程序高度可变。有些在祖细胞衍生的成红细胞中仅产生稍微过量的 HbF，而另一些则具有极高的 HbF 程序。目前尚不清楚这种变异性的分子基础。
The absolute adult and fetal hemoglobin (HbF) contents of the erythroid cells derived from the differentiation of normal human and simian erythroid progenitors and of the peripheral blood erythroid burst-forming units (BFU-E) of patients with nondeletion hemoglobinopathies have been measured with a sensitive radioligand immunoassay. The HbF content varied between 0.13 and 2.96 pg/cell, representing between 0.7% and 19.6% of the total hemoglobin with a mean value of 7.0%. The absolute content of HbF was indistinguishable in the well-hemoglobinized progeny of marrow erythroid colony-forming units, marrow or blood BFU-E, or of mixed colony-forming units. The term HbF program refers to this inherent capacity to produce fetal hemoglobin (HbF) in the erythroid cells derived from these progenitors in vitro. The HbF content of marrow erythroblasts as determined by the same radioligand immunoassay was similar to that found in the peripheral blood, suggesting that the switch off of gamma-chain production occurs after the erythroid colony-forming unit stage of maturation. Increasing concentrations of a crude erythropoietin-containing preparation induced higher numbers of erythroid colonies, which were larger in size, but the HbF program was unaffected. In contrast to the hemoglobin accumulation in human progenitor-derived colonies, simian progenitor-derived colonies produced considerably more HbF, and the amount of HbF was strongly influenced by progenitor maturity. Assays of the HbF content of erythroblasts derived from culture of the peripheral blood BFU-E of patients with nondeletion hemoglobinopathies and their parents showed that the HbF program in the progenitors of such patients is highly variable. Some produce only a slight excess of HbF in progenitor-derived erythroblasts, whereas others have extraordinarily high HbF programs. The molecular basis of this variability is presently unknown.Images