Developmental regulation of erythropoiesis by hematopoietic growth factors: analysis on populations of BFU-E from bone marrow, peripheral blood, and fetal liver.

Developmental regulation of erythropoiesis by hematopoietic growth factors: analysis on populations of BFU-E from bone marrow, peripheral blood, and fetal liver.
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DOI:
10.1182/blood.v74.1.49.49
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发表时间:
1989
期刊:
影响因子:
20.3
通讯作者:
S. Emerson;S. Thomas;J. Ferrara;J. Greenstein
S. Emerson;S. Thomas;J. Ferrara;J. Greenstein
中科院分区:
医学1区
文献类型:
--
作者:
S. Emerson;S. Thomas;J. Ferrara;J. Greenstein

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胎儿造血的特征在于扩大红细胞生成以支持持续增加的RBC质量。为了探索这种合成代谢、非稳态红细胞生成的基础,比较了重组造血生长因子对来自胎儿和成人组织的高度富集的造血祖细胞的增殖作用。与成人骨髓(BM)或外周血(PB)BFU-E不同,胎肝BFU-E在不添加GM集落刺激因子(GM-CSF)或白细胞介素-3(IL-3)的情况下能够响应促红细胞生成素而增殖,促红细胞生成素(Epo)直接刺激悬浮培养中胎儿BFU-E池的扩增。针对富集的胎肝祖细胞产生了鼠单克隆抗体(MoAb)Ep 3,该抗体可检测所有的胎儿BFU-E,并与成人BM BFU-E和CFU-E的促红细胞生成素反应性、GM-CSF/IL-3非依赖性部分反应。所有成人PB BFU-E均为Ep 3-,但经GM-CSF或IL-3刺激后变为Ep 3+。这些数据表明,Epo在胎儿肝红细胞生成中起着独特的作用,除了促进后期红系祖细胞的终末分化外,还刺激未成熟BFU-E的增殖。此外,这些结果证明了检测所有促红细胞生成素反应性祖细胞并区分成人BM和PB中的BFU-E区室的MoAb。
Fetal hematopoiesis is characterized by expanding erythropoiesis to support a continuously increasing RBC mass. To explore the basis for this anabolic, nonhomeostatic erythropoiesis, the proliferative effect of recombinant hematopoietic growth factors on highly enriched hematopoietic progenitor cells from fetal and adult tissues were compared. Fetal hepatic BFU-E, unlike adult bone marrow (BM) or peripheral blood (PB) BFU-E, were capable of proliferating in response to erythropoietin in the absence of added GM colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and erythropoietin (Epo) directly stimulated the expansion of the fetal BFU-E pool in suspension culture. A murine monoclonal antibody (MoAb), Ep 3, was raised against enriched fetal liver progenitor cells, which detected all fetal BFU-E and which reacted with the erythropoietin-responsive, GM-CSF/IL-3-independent fraction of adult BM BFU-E and CFU-E. All adult PB BFU-E were Ep 3- but became Ep 3+ after stimulation with GM-CSF or IL-3. These data indicate that Epo plays a unique role in fetal hepatic erythropoiesis, stimulating proliferation of immature BFU-E in addition to promoting terminal differentiation of later erythroid progenitor cells. In addition, these results demonstrate a MoAb which detects all erythropoietin-responsive progenitor cells and distinguishes the BFU-E compartments in adult BM and PB.