Weinberg R S, Acosta R, Knobloch M E, Garber M, Alter B P
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Hemoglobin. 1995 Sep;19(5):263-75. doi: 10.3109/03630269509005813.
Erythropoiesis is increased in cultures of human blood progenitors when oxygen tension is reduced from 20% (room air) to 5% (low oxygen, closer to physiological bone marrow levels). The effects of low oxygen on gamma-globin synthesis and colony growth in methyl cellulose cultures of blood mononuclear cells from normal individuals and patients with sickle cell diseases were examined. Low oxygen increased colony numbers by 1.5- to 2-fold and erythropoietin sensitivity by almost 2-fold. The interval required for maximal colony growth in cultures from patients with sickle cell disease (sickle colonies) was reduced from 17 days in 20% oxygen to 13 days in 5% oxygen. Relative synthesis of gamma-globin was examined by labeling with 3H-leucine and electrophoresis on Triton acid urea polyacrylamide gels. The % gamma was 1.7-fold higher in normal and 1.4-fold higher in sickle cultures on day 13 in low oxygen. On day 16 the expected temporal decline was not seen in low oxygen, and the % gamma was 2-fold higher in normal and 1.8-fold higher in the sickle studies. Hemin increased colony growth and gamma-globin synthesis in normal cultures in air, and the effects of hemin and low oxygen were additive. In sickle cultures, hemin and low oxygen had additive effects on colony growth, but only low oxygen increased gamma-globin synthesis. Interleukin-3 increased colony numbers on day 13, primarily by acceleration of peak growth. Interleukin-3 also increased gamma-globin synthesis in low oxygen in normal but not sickle cultures. Thus, low oxygen increases in vitro sensitivity to erythropoietin, colony numbers, and relative gamma-globin synthesis in normal and sickle cultures.
当氧张力从20%（室内空气）降至5%（低氧，更接近生理性骨髓水平）时，人类血液祖细胞培养物中的红细胞生成增加。研究了低氧对正常个体和镰状细胞病患者血液单核细胞甲基纤维素培养物中γ-珠蛋白合成和集落生长的影响。低氧使集落数量增加了1.5至2倍，促红细胞生成素敏感性增加了近2倍。镰状细胞病患者培养物（镰状集落）中最大集落生长所需的时间间隔从20%氧浓度下的17天缩短至5%氧浓度下的13天。通过用³H-亮氨酸标记并在Triton酸性尿素聚丙烯酰胺凝胶上进行电泳来检测γ-珠蛋白的相对合成。在低氧条件下培养13天时，正常培养物中的γ-珠蛋白百分比高1.7倍，镰状细胞培养物中高1.4倍。在第16天，低氧条件下未观察到预期的时间性下降，正常研究中γ-珠蛋白百分比高2倍，镰状细胞研究中高1.8倍。氯化血红素增加了空气中正常培养物中的集落生长和γ-珠蛋白合成，氯化血红素和低氧的作用具有相加性。在镰状细胞培养物中，氯化血红素和低氧对集落生长具有相加作用，但只有低氧增加了γ-珠蛋白合成。白细胞介素-3在第13天增加了集落数量，主要是通过加速峰值生长实现的。白细胞介素-3在低氧条件下也增加了正常培养物而非镰状细胞培养物中的γ-珠蛋白合成。因此，低氧增加了正常和镰状细胞培养物对促红细胞生成素的体外敏感性、集落数量以及相对γ-珠蛋白合成。
