Miller B A, Perrine S P, Bernstein A, Lyman S D, Williams D E, Bell L L, Olivieri N F
Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Blood. 1992 Apr 1;79(7):1861-8.
A new hematopoietic growth factor (Steel factor) has been identified which stimulates erythroid proliferation both in vitro and in vivo. We evaluated the influence of recombinant Steel factor on hemoglobin synthesis in peripheral blood (PB) BFU-E-derived cells from normal donors by radioimmunoassay (RIA) and compared it with stimulation with GM-CSF and interleukin-3 (IL-3). Only Steel factor stimulated a significant increase in BFU-E-derived colony size and a significant increase in fetal hemoglobin (HbF) in BFU-E-derived erythroblasts from 0.49% +/- 0.27% to 6.33% +/- 1.11% in serum-deprived media and from 1.88% +/- 0.24% to 11.17% +/- 0.91% in serum. To determine whether this influence on hemoglobinization also occurred in sickle cell disease, we studied 13 patients with sickle cell disease. In serum-deprived conditions, there was a significant increase in the number and size of BFU-E-derived colonies with Steel factor that was dose-dependent. In addition, the proportion of HbF in progenitor-derived cells increased by 66% from 4.1% +/- 0.6% to 6.8% +/- 1.2% with Steel factor. In serum-containing conditions studied in 12 patients, the increase in percentage of HbF was even greater, from 10.7% +/- 0.9% in control cultures to 22.5% +/- 2.6% with Steel factor. These increases in percentage of HbF were significant and dose-dependent. An increase in percentage of HbF was observed in erythroblasts harvested on day 11, 14, and 18 of culture. A decrease in mean picograms of total Hb per cell after coculture with Steel factor was noted, suggesting that growth kinetics influenced complete hemoglobinization. In serum-deprived conditions, picograms of HbF per cell was not affected by Steel factor, and in serum-containing conditions that augment in vitro HbF production it was enhanced. Thus, Steel factor stimulated a significant increase in percentage of HbF in erythroid cells from normal donors and patients with SCA in vitro.
一种新的造血生长因子（Steel因子）已被鉴定出来，它在体外和体内均能刺激红系增殖。我们通过放射免疫分析（RIA）评估了重组Steel因子对正常供体外周血（PB）中BFU-E来源细胞血红蛋白合成的影响，并将其与GM-CSF和白细胞介素-3（IL-3）的刺激作用进行了比较。只有Steel因子能显著增加BFU-E来源的集落大小，并且在血清饥饿培养基中，BFU-E来源的成红细胞中胎儿血红蛋白（HbF）从0.49%±0.27%显著增加至6.33%±1.11%，在有血清的情况下从1.88%±0.24%增加至11.17%±0.91%。为了确定这种对血红蛋白化的影响在镰状细胞病中是否也会发生，我们研究了13例镰状细胞病患者。在血清饥饿条件下，Steel因子使BFU-E来源的集落数量和大小显著增加，且呈剂量依赖性。此外，祖细胞来源细胞中HbF的比例在Steel因子作用下从4.1%±0.6%增加了66%至6.8%±1.2%。在对12例患者进行的含血清条件研究中，HbF百分比的增加更大，从对照培养中的10.7%±0.9%增加至Steel因子作用下的22.5%±2.6%。这些HbF百分比的增加是显著的且呈剂量依赖性。在培养第11、14和18天收获的成红细胞中观察到HbF百分比增加。与Steel因子共培养后，每个细胞总Hb的平均皮克数有所下降，这表明生长动力学影响了完全血红蛋白化。在血清饥饿条件下，每个细胞的HbF皮克数不受Steel因子影响，而在增强体外HbF产生的含血清条件下则有所增加。因此，Steel因子在体外能显著增加正常供体和镰状细胞贫血患者红系细胞中HbF的百分比。
