Phorbol ester effect on differentiation of human myeloid leukemia cell lines blocked at different stages of maturation.
Phorbol ester effect on differentiation of human myeloid leukemia cell lines blocked at different stages of maturation.
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发表时间：
1981-03
期刊：
影响因子：
11.2
通讯作者：
H. Koeffler;M. Bar‐eli;M. Territo
中科院分区：
文献类型：
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作者：
H. Koeffler;M. Bar‐eli;M. Territo
以不同成熟阶段阻断的人髓系白血病细胞株及其亚系为材料，研究了12-O-十四酰佛波醇-13-乙酸酯(TPA)等促癌佛波酯对细胞分化的调控作用。被阻断在成髓细胞-早幼粒细胞成熟期的髓系白血病细胞(KG-1、HL-60和ML-3)在与TPA共同培养时有显著的反应。细胞贴壁，出现伪足，光镜下显示巨噬细胞特征，出现非特异性酸性酯酶活性，吞噬酵母，硝基蓝四氮唑轻微减少，显示Fc-免疫球蛋白G受体，并杀菌。随着巨噬细胞的分化，溶菌酶的分泌和β-葡萄糖醛酸酶和酸性磷酸酶的活性增加了2-20倍。未分化成熟的髓系白血病细胞(KG-1a和K562)对TPA诱导的巨噬细胞分化完全抵抗。我们检测了接触佛波醇双酯后髓系细胞系和亚系的十种巨噬细胞功能。阻断在成髓细胞-早幼粒细胞成熟阶段的白血病细胞株几乎表达了所有巨噬细胞特有的功能。佛波醇双酯可能通过共同的细胞机制诱导分化，因为巨噬细胞分化事件不能分离。与之形成鲜明对比的是，早期髓系原始细胞(KG-1a和K562)在接触佛波二酯后不能获得任何巨噬细胞特异性功能。特别是KG-1a变异体，应该提供一个很好的模型来帮助阐明在接触佛波二酯期间控制巨噬细胞功能表达的调节机制。
The control of differentiation by tumor-promoting phorbol diesters including 12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated using cells from human myeloid leukemia lines and sublines that were blocked at different stages of maturation. The myeloid leukemia cells that were blocked at the myeloblast-promyelocyte stage of maturation (KG-1, HL-60, and ML-3) had a prominent response when cultured with TPA. The cells became adherent, developed pseudopodia, displayed macrophage characteristics by light microscopy, developed nonspecific acid esterase activity, phagocytized yeast, slightly reduced nitro blue tetrazolium, displayed Fc-immunoglobulin G receptors, and killed bacteria. Lysozyme secretion and enzyme activity for beta-glucuronidase and acid phosphatase increased 2- to 20-fold concomitant with macrophage differentiation. The myeloid leukemia cells that were blocked at the undifferentiated myeloid blast stage of maturation (KG-1a and K562) were completely resistant to TPA-induced macrophage differentiation. We examined ten macrophage functions in the myeloid cell lines and sublines after exposure to phorbol diesters. The leukemic lines blocked at the myeloblast-promyelocyte stage of maturation expressed almost all the macrophage-specific functions. Phorbol diesters probably induced differentiation through a common cellular mechanism because the macrophage-differentiated events could not be dissociated. In sharp contrast, the early myeloid blast cells (KG-1a and K562) were incapable of acquiring any of the macrophage-specific functions after exposure to phorbol diesters. The KG-1a variant, in particular, should provide a good model to help elucidate the regulatory mechanism controlling the expression of macrophage functions during exposure to phorbol diesters.