CYCLIC NUCLEOTIDE-INDUCED MATURATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELLS
CYCLIC NUCLEOTIDE-INDUCED MATURATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELLS
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DOI：
10.1172/jci110707
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发表时间：
1982-01-01
影响因子：
15.9
通讯作者：
NIEDEL, JE
中科院分区：
文献类型：
--
作者：
CHAPLINSKI, TJ;NIEDEL, JE
髓细胞体外分化的特点是成熟的形态学、功能和生化标记的顺序出现。研究了增加细胞内cAMP浓度的药物对人早幼粒细胞白血病细胞（HL60）这些标志物表达的影响。用500 .mu处理细胞。mn6、o2 -二丁基- camp表达甲酰基肽和补体受体，减少硝基蓝四氮唑，粘附于底物，表现出趋化性，刺激溶酶体酶释放，迅速停止增殖，呈现髓细胞和超髓细胞形态。前列腺素E2 （100 nM）和茶碱（500 .mu）。M)诱导了类似的功能变化，但细胞在髓细胞期后未成熟。霍乱毒素（1 nM或50 nM）诱导甲酰基肽受体的表达和粘附，但细胞不减少硝基蓝四唑，继续增殖，形态不变。甲酰基肽受体的表达是这些成熟修饰程序的最早标志。受体在处理后2 h内出现，并在72 h内线性增加。受体的表达依赖于新蛋白的合成。48 h时，Scatchard分析显示2.4次。105个受体/细胞，KD为1.3 nM。与二甲亚砜、视黄酸或肉豆酸酯诱导的HL60分化相反，提高细胞内cAMP的药物启动的发育程序有几个独特的特征：质膜成熟与形态成熟分离；诱导后无明显潜伏期；最早的膜标记在2 h内表达；终端差异化的承诺被推迟。
Myeloid differentiation in vitro is characterized by the sequential appearance of morphological, functional and biochemical markers of maturation. The effect was examined of agents that increased the intracellular cAMP concentration on the expression of these markers by human promyelocytic leukemia cells (HL60). Cells treated with 500 .mu.M N6,O2-dibutyryl-cAMP expressed formyl peptide and complement receptors, reduced nitroblue tetrazolium, adhered to substrate, demonstrated chemotaxis and stimulated lysosomal enzyme release, rapidly ceased proliferation and assumed the morphology of myelocytes and metamyelocytes. Prostaglandin E2 (100 nM) and theophylline (500 .mu.M) induced similar functional changes but the cells did not mature beyond the myelocyte stage. Cholera toxin (1 or 50 nM) induced formyl-peptide receptor expression and adherence but the cells did not reduce nitroblue tetrazolium, continued to proliferate and were unchanged morphologically. Formyl-peptide receptor expression was the earliest marker of these modified programs of maturation. The receptor appeared within 2 h after treatment and increased linearly for 72 h. Receptor expression was dependent on new protein synthesis. At 48 h, Scatchard analysis demonstrated 2.4 .times. 105 receptors/cell with a KD of 1.3 nM. In contrast to induction of HL60 differentiation by dimethyl sulfoxide, retinoic acid or phorbol myristate acetate, the developmental programs initiated by agents that raised intracellular cAMP shared several unique features: plasma membrane maturation was dissociated from morphological maturation; no latent period was evident following induction; the earliest membrane marker was expressed within 2 h; commitment to terminal differentiation was delayed.