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白细胞介素-3、粒细胞巨噬细胞集落刺激因子及粒细胞集落刺激因子受体在细胞系及原发性白血病细胞上的表达:受体异质性及其与生长因子反应性的关系

Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness.

作者信息

Park L S, Waldron P E, Friend D, Sassenfeld H M, Price V, Anderson D, Cosman D, Andrews R G, Bernstein I D, Urdal D L

机构信息

Department of Biochemistry, Immunex Corporation, Seattle, WA 98101.

出版信息

Blood. 1989 Jul;74(1):56-65.

PMID:2473802
Abstract

Recombinant human granulocyte-macrophage (GM) colony-stimulating factor (GM-CSF), G-CSF, and interleukin-3 (IL-3) labeled with 125I were used to study the characteristics and distribution of receptors for these factors on in vitro cell lines and on cells from patients with acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). Receptors for GM-CSF and G-CSF were restricted to a subset of myelomonocytic cell lines whereas IL-3 receptors were also found on pre-B- or early B-cell lines. Receptors for all three CSFs were broadly distributed on ANL cells, with considerable variability in levels of expression. Measurement of the colony-forming ability of ANL cells in response to the CSFs showed that there was no direct correlation between the ability of the cells to respond to a growth factor and the absolute number of receptors expressed for that growth factor. Binding of radiolabeled IL-3 and GM-CSF to ANL cells produced complex biphasic curves. Further analysis showed that both IL-3 and GM-CSF were able to partially compete for specific binding of the heterologous radiolabeled ligand to cells from several ANL patients, suggesting that heterogeneity may exist in human CSF receptors. These results provide new insights into the complex role that CSFs may play in ANL.

摘要

用125I标记的重组人粒细胞-巨噬细胞(GM)集落刺激因子(GM-CSF)、粒细胞集落刺激因子(G-CSF)和白细胞介素-3(IL-3),研究这些因子在体外细胞系以及急性非淋巴细胞白血病(ANL)和急性淋巴细胞白血病(ALL)患者细胞上的受体特征和分布。GM-CSF和G-CSF的受体仅限于骨髓单核细胞系的一个亚群,而IL-3受体也存在于前B或早期B细胞系上。所有三种集落刺激因子(CSF)的受体广泛分布于ANL细胞,表达水平存在相当大的变异性。检测ANL细胞对CSF的集落形成能力表明,细胞对生长因子的反应能力与该生长因子表达的受体绝对数量之间没有直接相关性。放射性标记的IL-3和GM-CSF与ANL细胞的结合产生复杂的双相曲线。进一步分析表明,IL-3和GM-CSF都能够部分竞争异源放射性标记配体与几名ANL患者细胞的特异性结合,这表明人CSF受体可能存在异质性。这些结果为CSF在ANL中可能发挥的复杂作用提供了新的见解。

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