UP-REGULATION OF LINEAGE-SPECIFIC RECEPTORS AND LIGANDS IN MULTIPOTENTIAL PROGENITOR CELLS IS PART OF AN ENDOGENOUS PROGRAM OF DIFFERENTIATION
UP-REGULATION OF LINEAGE-SPECIFIC RECEPTORS AND LIGANDS IN MULTIPOTENTIAL PROGENITOR CELLS IS PART OF AN ENDOGENOUS PROGRAM OF DIFFERENTIATION
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DOI：
10.3109/08977199308991589
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发表时间：
1993-01-01
期刊：
影响因子：
1.8
通讯作者：
OSTERTAG, W
中科院分区：
文献类型：
--
作者：
JUST, U;FRIEL, J;OSTERTAG, W
用表达GM-CSF基因的逆转录病毒载体感染的多能造血祖细胞系（FDCP-Mix）在IL-3中维持时显示GM-CSF受体的功能下调，并且在IL-3撤除时受体的激活导致同步分化成成熟粒细胞和巨噬细胞。这个系统现在已经被用来研究是否其他一些生长因子的受体也受到分化的影响。我们在这里显示，无论分化是否由GM-CSF或其他条件诱导，M-CSF、G-CSF和促红细胞生成素的谱系特异性受体都上调。伴随诱导编码配体M-CSF和G-CSF但不编码促红细胞生成素的mRNA，表明M-CSF和可能的G-CSF通过谱系特异性受体的自分泌刺激促进巨噬细胞或粒细胞分化。暴露于GM-CSF时分化能力被阻断但仍需要GM-CSF增殖的FDCP Mix突变体不表达增加水平的M-CSF受体或M-CSF。基于这些数据，我们认为这些谱系特异性受体的表达是髓系分化的内在内源性程序的一部分。
Multipotent hematopoietic progenitor cell lines (FDCP-Mix) infected with a retroviral vector expressing the GM-CSF gene show functional downregulation of the GM-CSF receptor when maintained in IL-3 and activation of the receptor resulting in synchronous differentiation into mature granulocytes and macrophages on withdrawal of IL-3. This system has now been used to investigate whether or not receptors for some of the other growth factors are also influenced as a consequence of differentiation. We show here the lineage specific receptors for M-CSF, G-CSF and erythropoietin are all upregulated, regardless of whether or not differentiation is induced by GM-CSF or by other conditions. Concomitant induction of the mRNA coding for the ligands M-CSF and G-CSF, but not for erythropoietin, suggests that M-CSF and possibly G-CSF facilitate macrophage or granulocyte differentiation by an autocrine stimulation of the lineage specific receptors. FDCP Mix mutants that are blocked in their ability to differentiate on exposure to GM-CSF, but that still require GM-CSF for proliferation, do not express increased levels of M-CSF receptor nor M-CSF. Based on these data, we suggest that expression of these lineage specific receptors is part of the intrinsic endogenous program of myeloid differentiation.