BASIC FIBROBLAST GROWTH-FACTOR MEDIATES ITS EFFECTS ON COMMITTED MYELOID PROGENITORS BY DIRECT ACTION AND HAS NO EFFECT ON HEMATOPOIETIC STEM-CELLS
BASIC FIBROBLAST GROWTH-FACTOR MEDIATES ITS EFFECTS ON COMMITTED MYELOID PROGENITORS BY DIRECT ACTION AND HAS NO EFFECT ON HEMATOPOIETIC STEM-CELLS
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DOI：
10.1182/blood.v86.6.2123.bloodjournal8662123
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发表时间：
1995-09-15
期刊：
影响因子：
20.3
通讯作者：
SCADDEN, DT
中科院分区：
文献类型：
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作者：
BERARDI, AC;WANG, AL;SCADDEN, DT
碱性成纤维细胞生长因子或成纤维细胞生长因子-2（FGF）已显示影响骨髓细胞增殖，并假设刺激原始造血细胞。我们试图评估FGF对造血干细胞的作用，并确定FGF是否直接或通过诱导其他细胞因子介导其对祖细胞的作用。为了解决FGF的直接作用，我们研究了FGF是否通过两种类型的辅助细胞（骨髓（BM）成纤维细胞和巨噬细胞）诱导白细胞介素-1 β（IL-1 β）、肿瘤坏死因子α IL-6、粒细胞集落刺激因子或粒细胞-巨噬细胞集落刺激因子的产生。我们进一步评估了FGF诱导的细胞因子的抗体是否影响集落形成。为了确定FGF是否能够刺激多能祖细胞，我们评估了BM单核细胞（BMMC）或CD 34（+）BMMC刺激后不同集落类型的输出，并比较了FGF与干细胞活性细胞因子kit配体（KL）的作用。此外，一个子集的CD 34 + BMMC的造血干细胞的特征进行了分离的功能选择和他们对FGF的反应进行了评估，使用增殖，集落形成，和单细胞聚合酶链反应（PCR）测定。我们确定FGF对单个细胞因子IL-6的产生具有刺激作用，但FGF对集落形成的影响并不归因于该诱导。FGF在体外对骨髓祖细胞的作用比KL更受限制，对红系集落形成没有影响。通过单细胞逆转录PCR评估，FGF不刺激干细胞，并且在干细胞上未检测到FGF受体。相比之下，FGF受体基因表达检测髓系祖细胞群体。这些数据支持FGF的直接介导作用，其似乎仅限于谱系定型的骨髓祖细胞。成纤维细胞生长因子似乎不调节人类造血干细胞。(C)1995年，美国血液学会。
Basic fibroblast growth factor or fibroblast growth factor-2 (FGF) has been shown to affect myeloid cell proliferation and hypothesized to stimulate primitive hematopoietic cells. We sought to evaluate the effect of FGF on hematopoietic stem cells and to determine if FGF mediated its effects on progenitor cells directly or through the induction of other cytokines. To address the direct effects of FGF, we investigated whether FGF induced production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha IL-6, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor by two types of accessory cells, bone marrow (BM) fibroblasts and macrophages. We further evaluated whether antibodies to FGF-induced cytokines affected colony formation, To determine if FGF was capable of stimulating multipotent progenitors, we assessed the output of different colony types after stimulation of BM mononuclear cells (BMMC) or CD34(+) BMMC and compared the effects of FGF with the stem cell active cytokine, kit ligand (KL). In addition, a subset of CD34+ BMMC with characteristics of hematopoietic stem cells was isolated by functional selection and their response to FGF was evaluated using proliferation, colony-forming, and single-cell polymerase chain reaction (PCR) assays. We determined that FGF had a stimulatory effect on the production of a single cytokine, IL-6, but that the effects of FGF on colony formation were not attributable to that induction. FGF was more restricted in its in vitro effects on BM progenitors than KL was, having no effect on erythroid colony formation. FGF did not stimulate stem cells and FGF receptors were not detected on stem cells as evaluated by single-cell reverse transcription PCR. In contrast, FGF receptor gene expression was detected in myeloid progenitor populations. These data support a directly mediated effect for FGF that appears to be restricted to lineage-committed myeloid progenitor cells. FGF does not appear to modulate the human hematopoietic stem cell. (C) 1995 by The American Society of Hematology.