Croizat H, Nagel R L
Division of Hematology, Albert Einstein College of Medicine, Bronx, New York 10461.
Br J Haematol. 1993 Jul;84(3):481-91. doi: 10.1111/j.1365-2141.1993.tb03105.x.
Sickle cell anaemia (SS) patients with low (< 9%) HbF levels (LFSS) are characterized by an increased number of circulating BFU-E in active DNA synthesis, and release of burst promoting activity (BPA) by unstimulated low density (LD) adherent cells. In contrast, circulating BFU-E from SS patients with high (> 9%) HbF levels (HFSS) are normal in number, largely in resting phase, and their LD cells do not release BPA-like activity. We report now that in LFSS patients, adherent cell depletion decreases BFU-E growth in culture and apparent BFU-E cycling. Furthermore, addition of conditioned media (CM) from LD cells of LFSS patients restored cycling BFU-E expression in culture. Neutralization analysis with anti-GM-CSF antibody demonstrated that GM-CSF is, at least, one factor responsible for BPA activity present in this CM. Thus, GM-CSF is constitutively produced by unstimulated monocytes in LFSS patients. In contrast, HFSS patients' adherent cell depletion increases cycling of BFU-E in culture. CM from HFSS patients inhibits BFU-E expression in culture. Hence, LD adherent cells from HFSS patients may release a yet unknown inhibitor factor(s). In addition, we report a distinct response pattern in SS patients' BFU-E to growth factor (GM-CSF, IL-3): (a) LFSS patients have a BFU-E population, equally responsive to GM-CSF and IL-3; (b) HFSS patients, have a subset of BFU-E exclusively dependent on IL-3 (20-40% of the circulating BFU-E). This pattern is very similar to that of normal BFU-E. In conclusion, BFU-E from LFSS patients represent an actively proliferating population, equally responsive to GM-CSF and IL-3, controlled by constitutively produced GM-CSF, suggesting a unique BFU-E behaviour in SS patients with low HbF levels and high haemopoietic stress. The heterogeneous regulation of BFU-E in SS disease seems to be the epiphenomenon of HbF levels, and not vice versa.
血红蛋白F（HbF）水平低（<9%）的镰状细胞贫血（SS）患者（LFSS）的特征是，处于活跃DNA合成状态的循环爆式红系集落形成单位（BFU-E）数量增加，且未受刺激的低密度（LD）贴壁细胞释放爆式促进活性（BPA）。相比之下，HbF水平高（>9%）的SS患者（HFSS）的循环BFU-E数量正常，大多处于静止期，且其LD细胞不释放BPA样活性。我们现在报告，在LFSS患者中，去除贴壁细胞会降低培养中BFU-E的生长以及明显的BFU-E循环。此外，添加来自LFSS患者LD细胞的条件培养基（CM）可恢复培养中循环BFU-E的表达。用抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）抗体进行的中和分析表明，GM-CSF至少是该CM中存在的BPA活性的一个 responsible因素。因此，GM-CSF由LFSS患者未受刺激的单核细胞组成性产生。相比之下，HFSS患者去除贴壁细胞会增加培养中BFU-E的循环。HFSS患者的CM抑制培养中BFU-E的表达。因此，HFSS患者的LD贴壁细胞可能释放一种未知的抑制因子。此外，我们报告了SS患者的BFU-E对生长因子（GM-CSF、白细胞介素-3（IL-3））的一种独特反应模式：（a）LFSS患者有一群BFU-E，对GM-CSF和IL-3的反应相同；（b）HFSS患者有一部分BFU-E仅依赖IL-3（占循环BFU-E的20 - 40%）。这种模式与正常BFU-E的模式非常相似。总之，LFSS患者的BFU-E代表一个活跃增殖的群体，对GM-CSF和IL-3的反应相同，受组成性产生的GM-CSF控制，这表明HbF水平低且造血应激高的SS患者中BFU-E具有独特行为。SS病中BFU-E的异质性调节似乎是HbF水平的附带现象，而非相反。 （原文中“responsible”前多了个“a”，翻译时按正确理解翻译）
