Paul C C, Tolbert M, Mahrer S, Singh A, Grace M J, Baumann M A
Research Service, Dayton VA Medical Center, OH 45428.
Blood. 1993 Mar 1;81(5):1193-9.
The cytokines interleukin-3 (IL-3); IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are known to contribute to the proliferation and differentiation of eosinophil progenitors. Recently, it was determined that the cellular receptors for these three cytokines share a common beta-chain while having unique alpha-chains. Thus, there is considerable interest in how these cytokines and their receptors interact in promoting production of eosinophils. We have established a cell line (AML14) from a patient with acute myelogenous leukemia that will consistently exhibit eosinophilic differentiation in suspension in response to IL-3, IL-5, and GM-CSF. Proliferation with only modest differentiative effects was observed in response to a single cytokine. Combinations of two cytokines gave variable results, with GM-CSF + IL-3 and IL-3 + IL-5 causing more proliferation than a single cytokine but little more differentiation. The combination of GM-CSF + IL-5 caused marked enhancement of eosinophilic differentiation with only modest augmentation of proliferation. The combination of all three cytokines was most effective in stimulating both proliferation and eosinophilic differentiation (up to 70% of cells) of AML14 cells. Specific binding of GM-CSF and IL-5 to AML14 cells can be conveniently studied by flow cytometric methods, and cross-competition of these two cytokines for their respective receptors was demonstrated. IL-3 was shown to partially compete for IL-5 binding on AML14 cells. Although specific IL-3 binding could not be demonstrated by flow cytometry, mRNA for the alpha-chains of the IL-3, IL-5, and GM-CSF receptors and the beta-chain common to all three receptors was detected in AML14 cells. The AML14 cell line may be a useful model for the study of cooperative interactions of IL-3, IL-5, GM-CSF, and their respective receptors in the promotion of eosinophil progenitor growth and differentiation.
细胞因子白细胞介素-3（IL-3）、IL-5和粒细胞-巨噬细胞集落刺激因子（GM-CSF）已知有助于嗜酸性粒细胞祖细胞的增殖和分化。最近发现，这三种细胞因子的细胞受体共享一条共同的β链，同时具有独特的α链。因此，人们对这些细胞因子及其受体如何相互作用以促进嗜酸性粒细胞的产生非常感兴趣。我们从一名急性髓性白血病患者中建立了一个细胞系（AML14），该细胞系在悬浮培养中对IL-3、IL-5和GM-CSF会持续表现出嗜酸性分化。对单一细胞因子的反应观察到增殖但分化作用适度。两种细胞因子的组合产生了不同的结果，GM-CSF + IL-3和IL-3 + IL-5比单一细胞因子引起更多的增殖，但分化增加不多。GM-CSF + IL-5的组合导致嗜酸性分化显著增强，而增殖仅适度增加。三种细胞因子的组合在刺激AML14细胞的增殖和嗜酸性分化（高达70%的细胞）方面最有效。GM-CSF和IL-5与AML14细胞的特异性结合可以通过流式细胞术方便地研究，并且证明了这两种细胞因子对其各自受体的交叉竞争。IL-3被证明部分竞争AML14细胞上IL-5的结合。尽管通过流式细胞术无法证明特异性IL-3结合，但在AML14细胞中检测到了IL-3、IL-5和GM-CSF受体α链以及所有三种受体共同的β链的mRNA。AML14细胞系可能是研究IL-3、IL-5、GM-CSF及其各自受体在促进嗜酸性粒细胞祖细胞生长和分化中的协同相互作用的有用模型。
