Stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production and its role as an autocrine inducer of CD14 upregulation in human myeloid leukemia cells
Stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production and its role as an autocrine inducer of CD14 upregulation in human myeloid leukemia cells
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DOI：
10.1089/jir.1996.16.479
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发表时间：
1996-06-01
影响因子：
2.3
通讯作者：
Sonnenfeld, G
中科院分区：
文献类型：
--
作者：
Akin, C;Sonnenfeld, G
粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种多效细胞因子，参与正常造血细胞和白血病造血细胞的生长和分化。由于其在髓系白血病发病机制中的潜在意义，我们研究了导致人髓系白血病细胞系K-562分泌GM-CSF的细胞外刺激，并且已经证明了细胞因子在该细胞系的分化过程中的重要作用，发现TNF-α、IL-1 β、佛波醇酯（PMA）和钙离子载体A23187刺激K-562细胞产生GM-CSF，PMA导致细胞分化成巨核细胞谱系，而用A23187处理导致单核细胞/巨噬细胞标记物CD 14的表达增加，培养基中GM-CSF活性的中和，以及其受体的阻断，导致抑制CD 14表达的增加并部分恢复暴露于A23187的细胞的增殖能力，自分泌GM-CSF分泌似乎在PMA诱导的巨核细胞分化中没有发挥重要作用。这些结果表明，自分泌GM-CSF分泌可能与髓性白血病细胞的分化没有任何显着的生长刺激活性。
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that takes part in the growth and differentiation of normal and leukemic hematopoietic cells, Because of its potential significance in the etiopathogenesis of myeloid leukemia, we have studied the extracellular stimuli leading to GM-CSF secretion from a human myeloid leukemia cell line, K-562, and have demonstrated an important role for the cytokine in the differentiation process of this cell line, TNF-alpha, IL-1 beta, phorbol ester (PMA), and calcium ionophore A23187 were found to stimulate GM-CSF production from K-562 cells, PMA caused the cells to differentiate into megakaryocytic lineage, whereas treatment with A23187 resulted in increased expression of monocyte/macrophage marker CD14, Neutralization of the GM-CSF activity in the culture medium, as well as blocking of its receptors, resulted in suppression of the increase in CD14 expression and partially restored the proliferative capacity in cells exposed to A23187, Autocrine GM-CSF secretion did not appear to play an important role in PMA-induced megakaryocytic differentiation. These results suggest that autocrine GM-CSF secretion may be associated with differentiation of myeloid leukemic cells without any significant growth stimulatory activity.