Synergistic action of Flt3 and gp130 signalings in human hematopoiesis.
Synergistic action of Flt3 and gp130 signalings in human hematopoiesis.
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Flt3 和 gp130 信号在人类造血过程中的协同作用。
DOI：
10.1182/blood.v90.11.4363
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发表时间：
1997
期刊：
影响因子：
20.3
通讯作者：
T. Nakahata
中科院分区：
文献类型：
--
作者：
Y. Ebihara;K. Tsuji;S. Lyman;X. Sui;M. Yoshida;K. Muraoka;Kaoru Yamada;R. Tanaka;T. Nakahata
我们最近发现，c-kit信号与由白细胞介素（IL）-6和可溶性IL-6受体（IL-6/sIL-6 R）复合物介导的糖蛋白（gp）130信号协同刺激人原始造血祖细胞扩增和红细胞生成素非依赖性红细胞生成。在本研究中，我们研究了Flt 3的配体（FL），其受体酪氨酸激酶与c-kit密切相关，与IL-6/sIL-6 R联合对体外人造血的影响。在含血清甲基纤维素的脐血CD 34（+）细胞克隆培养中，FL单独使用仅能诱导粒-巨噬细胞（GM）集落形成，而FL与IL-6/sIL-6 R联合使用则能诱导GM集落形成，并能诱导红系爆发和混合集落形成，而单独使用IL-6/sIL-6 R则不能。在悬浮培养中，单独加入FL或IL-6/sIL-6 R时，CD 34（+）细胞产生少量髓样细胞。然而，IL-6/sIL-6 R的添加到与FL的培养物诱导产生了显着数量的红系细胞和巨核细胞，除了髓系细胞。FL和IL-6/sIL-6 R的组合也诱导了GM集落和红系爆发形成细胞和多能祖细胞的显着扩增，尽管FL或IL-6/sIL-6 R单独诱导仅少量GM集落祖细胞的产生。FL和IL-6/sIL-6 R的协同作用在无血清克隆和悬浮培养中得到证实。此外，抗人gp 130单克隆抗体的加入消除了协同作用。这些结果表明Flt 3信号以及c-kit信号与gp 130信号协同刺激人骨髓生成、红细胞生成和巨核细胞生成，以及原始多能造血祖细胞的扩增。
We recently showed that c-kit signal synergizes with glycoprotein (gp)130 signal mediated by a complex of interleukin (IL)-6 and soluble IL-6 receptor (IL-6/sIL-6R) to stimulate the expansion of human primitive hematopoietic progenitor cells and erythropoietin-independent erythropoiesis. In the present study, we examined the effect of a ligand for Flt3 (FL), whose receptor tyrosine kinase is closely related to c-kit, in combination with IL-6/sIL-6R on human hematopoiesis in vitro. In serum-containing methylcellulose clonal culture of cord blood CD34(+) cells, whereas FL alone stimulated only granulocyte-macrophage (GM) colony formation, erythroid bursts and mixed colonies in addition to GM colonies were induced by FL with IL-6/sIL-6R, but not IL-6/sIL-6R alone. In suspension culture, CD34(+) cells generated a small number of myeloid cells in the presence of FL or IL-6/sIL-6R alone. However, the addition of IL-6/sIL-6R to the culture with FL induced the generation of a significant number of erythroid cells and megakaryocytes in addition to myeloid cells. The combination of FL and IL-6/sIL-6R also induced a remarkable expansion of GM colony- and erythroid burst-forming cells and multipotential progenitors, although FL or IL-6/sIL-6R alone induced the generation of only a small number of progenitors for GM colonies. The synergistic effects of FL and IL-6/sIL-6R were confirmed in serum-free clonal and suspension cultures. In addition, the addition of anti-human gp130 monoclonal antibodies abrogated the synergistic action. These results indicate that Flt3 signal, as well as c-kit signal, synergizes with gp130 signal to stimulate human myelopoiesis, erythropoiesis and megakaryopoiesis, and the expansion of primitive multipotential hematopoietic progenitor cells.
影响因子：
20.3
作者：
M. Ogawa
通讯作者：
M. Ogawa
DOI：
10.1073/pnas.90.2.735
发表时间：
1993-01
影响因子：
11.1
作者：
H. Mitsui;T. Furitsu;A. Dvorak;A. Irani;L. Schwartz;Naoki Inagaki;M. Takei;K. Ishizaka;K. Zsebo;S. Gillis;T. Ishizaka
通讯作者：
H. Mitsui;T. Furitsu;A. Dvorak;A. Irani;L. Schwartz;Naoki Inagaki;M. Takei;K. Ishizaka;K. Zsebo;S. Gillis;T. Ishizaka