Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice
Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice
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DOI：
10.1182/blood.v87.11.4544.bloodjournal87114544
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发表时间：
1996-06-01
期刊：
影响因子：
20.3
通讯作者：
Ogawa, M
中科院分区：
文献类型：
--
作者：
Ku, H;Yonemura, Y;Ogawa, M
最近，MpI受体（ML）的配体被鉴定为血小板生成素，其是巨核细胞生成和血小板生成的主要调节剂。我们研究了ML作为单一因子或与早期作用因子如钢因子（SF）、白细胞介素（IL）-3、IL-11、IL-6和粒细胞集落刺激因子（G-CSF）组合对小鼠原始祖细胞集落形成的影响。通过Nycodenz密度梯度分离、免疫磁性选择谱系阴性细胞和荧光激活细胞分选仪（FAGS）分选Ly-6A/E（+）Kit（+）细胞的组合，从锂氟尿嘧啶（5-FU）处理小鼠的骨髓细胞中分离富集细胞周期休眠原始祖细胞的细胞。ML在促红细胞生成素的存在下，只能支持少数巨核细胞集落的形成。然而，ML与SF或IL-3协同作用以支持多种类型的造血集落（包括多谱系集落）的形成。ML和SF的组合对多能祖细胞的影响不通过其他细胞介导，如个别祖细胞的显微操作所示。在悬浮培养中，ML和SF的组合增加了多能祖细胞的数量。ML还与IL-11、IL-6或G-CSF协同作用，以支持在含血清培养物中而不是在无血清培养物中的集落形成。然而，在含血清培养物中观察到的多谱系集落形成通过添加针对Kit蛋白的中和抗体ACK 2而完全消除。对多能祖细胞集落发育的系列观察（作图研究）表明，ML触发了休眠祖细胞的细胞分裂。基于这些观察，我们提出ML可以作为一种早期作用的细胞因子，通过缩短细胞周期休眠祖细胞的G（0）期来刺激其增殖。(C)1996年，美国血液学会。
Recently, the ligand for the MpI receptor (ML) was identified to be thrombopoietin, the principal regulator of megakaryocytopoiesis and thrombopoiesis. We examined the effects of ML, as a single factor or in combinations with early acting factors such as steel factor (SF), interleukin (IL)-3, IL-ll, IL-6, and granulocyte colony-stimulating factor (G-CSF), on colony formation from primitive progenitors of mice. Cells enriched for cell cycle dormant primitive progenitors were isolated from bone marrow cells of li-fluorouracil (5-FU)-treated mice by a combination of Nycodenz density gradient separation, immunomagnetic selection for lineage-negative cells, and fluorescence-activated cell sorter (FAGS) sorting for Ly-6A/E(+)Kit(+) cells. ML, in the presence of erythropoietin, could support the formation of only a few megakaryocyte colonies. However, ML acted synergistically with SF or IL-3 to support the formation of multiple types of hematopoietic colonies including multilineage colonies. Effects of the combination of ML and SF on multipotential progenitors were not mediated through other cells, as demonstrated by micromanipulation of individual progenitors. In suspension culture, the combination of ML and SF increased the number of multipotential progenitors. ML also acted synergistically with IL-ll, IL-6, or G-CSF to support colony formation in serum-containing, but not in serum-free, cultures. However, the multilineage colony formation seen in serum-containing culture was completely abrogated by addition of ACK2, a neutralizing antibody to Kit protein. Serial observation (mapping studies) of colony development from multipotential progenitors suggested that ML triggers the cell division of dormant progenitors. Based on these observations, we propose that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G(0) period. (C) 1996 by The American Society of Hematology.