Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3':5'-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor.
Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3':5'-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor.
复制标题
用视黄酸引发人骨髓白血病细胞系 HL-60 和 U-937，以发挥环腺苷 3:5-单磷酸诱导剂和 T 淋巴细胞衍生分化因子的分化作用。
作者：
I. Olsson;T. Breitman;R. Gallo
人类细胞HL-60（急性早幼粒细胞白血病）和U-937（组织细胞单核细胞样淋巴瘤）在维甲酸（RA）的作用下分化为功能成熟的细胞。这种分化被已知的增加细胞内环腺苷3':5'-单磷酸（cAMP）水平的药物增强。目前的研究表明，这些细胞可以通过大约一天的RA治疗，然后暴露于camp诱导剂来诱导分化。相反的顺序无效。因此，HL-60可以在10 nM RA中孵育不到20小时，并对添加10 nM前列腺素E2或1 nM霍乱毒素产生分化反应，而单独添加10 nM RA几乎无活性。ra引发的HL-60也对t淋巴细胞衍生的分化诱导因子的浓度有分化反应，而t淋巴细胞衍生的分化诱导因子单独是无活性的。用100 nM RA孵育24小时后，U-937对camp诱导剂和分化诱导因子均有反应，而单独对其无活性。这些细胞系的启动不依赖于正常的蛋白质合成速率，因为在存在完全抑制生长的环己亚胺浓度的情况下，启动效果更好，这表明某些蛋白质合成的减少有利于ra诱导的分化。环己亚胺对HL-60有一定的引物作用，对U-937没有。HL-60，而不是U-937，对三磷酸腺苷和其他三磷酸核苷有反应，这与RA效应的调节可能通过质膜上的蛋白激酶活性介导的观点一致。研究发现，在成熟晚期被阻断的髓系，如HL-60和U-937，可以被RA引发对camp诱导剂和分化诱导因子的反应，这可能会提高我们对某些类型白血病典型的成熟停滞的理解。
The human cell lines HL-60 (acute promyelocytic leukemia) and U-937 (histiocytic monoblast-like lymphoma) differentiate to functionally mature cells by incubation with retinoic acid (RA). This differentiation is potentiated by agents known to increase intracellular cyclic adenosine 3':5'-monophosphate (cAMP) levels. The present study shows that these cells can be primed for differentiation by treatment for approximately one day with RA followed by exposure to a cAMP-inducing agent. The reverse sequence was ineffective. Thus, HL-60 could be primed by incubation for less than 20 hr with 10 nM RA to respond by differentiation to the addition of 10 nM prostaglandin E2 or 1 nM cholera toxin, whereas 10 nM RA alone was almost inactive. RA-primed HL-60 also responded with differentiation to a concentration of T-lymphocyte-derived differentiation-inducing factor which alone was inactive. U-937 primed by incubation for 24 hr with 100 nM RA responded to cAMP-inducing agents and differentiation-inducing factor, which alone were inactive on this cell line. Priming of these cell lines does not depend on the normal rate of protein synthesis, as it occurs even better in the presence of a concentration of cycloheximide that inhibits growth completely, suggesting that a decrease in synthesis of some protein(s) favors RA-induced differentiation. Cycloheximide alone produced some priming of HL-60 but not of U-937. HL-60, but not U-937, primed with RA responded to adenosine triphosphate and other nucleoside triphosphates, consistent with the notion that modulation of the RA effect may be mediated through protein kinase activity at the plasma membrane. The finding that myeloid cell lines, like HL-60 and U-937, blocked at a late stage of maturation can be primed by RA to respond to cAMP-inducing agents and differentiation-inducing factor may improve our understanding of the arrest in maturation typical of some forms of leukemia.