T and B leukemic cell lines exhibit different requirements for cell death: correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation and apoptosis in T cell lines but not in Burkitt's lymphoma
T and B leukemic cell lines exhibit different requirements for cell death: correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation and apoptosis in T cell lines but not in Burkitt's lymphoma
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DOI：
10.1038/sj.leu.2402401
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发表时间：
2002-04-01
期刊：
影响因子：
11.4
通讯作者：
Auberger, P
中科院分区：
文献类型：
--
作者：
Luciano, F;Ricci, JE;Auberger, P
细胞凋亡的执行阶段通过caspase的激活和功能发生，caspase裂解协调死亡过程的关键底物。在这里，我们比较了不同的T和B细胞系对死亡受体或星形孢子素诱导的细胞凋亡的敏感性。首先，我们发现死亡受体的表达与Fas或TRAIL的敏感性之间缺乏相关性。相反，在T细胞系中，caspase激活、DNA片段化和细胞死亡之间存在相关性。在T细胞中，CEM对Ch11反应发生了凋亡，但对Trail具有抵抗力，这与其表面缺乏Trail受体(DR4和DR5)是一致的。B细胞株SKW 6.4对CH11和星形孢菌素敏感，但对Trail耐药。由于B细胞株表达显著水平的DR4和DR5，SKW 6.4对Trail的抗性可能是由于诱骗受体DcR1的表达。Burkitt淋巴瘤，如RPMI8866和Raji对Ch11、Trail或星形孢子素没有表现出DNA片段化，但在效应器治疗后显示出长期依赖caspase的生存能力丧失。这项研究中使用的B细胞株表达非常弱或检测不到的DFF40水平和相对较高的DFF45水平。有趣的是，RPMI88.66的细胞液提取物，而不是其他B淋巴瘤的胞浆提取物，显示出依赖于细胞色素c的caspase激活水平的改变。综上所述，我们的结果表明：(1)死亡受体的表达与细胞凋亡的敏感性无关；(2)DFF40和DFF45的比例非常低本身不太可能解释为什么在某些B细胞系中观察到缺乏DNA片段化；(3)依赖细胞色素c的caspase激活缺陷可能至少部分解释了某些Burkitt淋巴瘤(RPMI88.66)对凋亡的不敏感性。因此，Burkitt淋巴瘤对凋亡的抵抗似乎不是由一般机制控制的，而是相当多的因素，并且在不同的细胞系之间是不同的。
The execution phase of apoptosis occurs through the activation and function of caspases which cleave key substrates that orchestrate the death process. Here, we have compared the sensitivity of various T and B cell lines to death receptor or staurosporine-induced apoptosis. First, we found a lack of correlation between death receptor expression and sensitivity to Fas or Trail. By contrast, a correlation between caspase activation, DNA fragmentation and cell death in T cell lines was evidenced. Among T cells, CEM underwent apoptosis in response to CH11 but were resistant to Trail in agreement with the absence of Trail receptors (DR4 and DR5) on their surface. The B cell line SKW 6.4 was sensitive to CH11 and staurosporine but resistant to Trail. As B cell lines expressed significant levels of DR4 and DR5, resistance to Trail in SKW 6.4 is likely due to the expression of the decoy receptor DcR1. Burkitt's lymphoma such as RPMI 8866 and Raji did not exhibit DNA fragmentation in response to CH11, Trail or staurosporine but showed long-term caspase-dependent loss of viability upon effector treatment. The B cell lines used in this study express very weak or undetectable levels of DFF40 and relatively high levels of DFF45. Interestingly, cytosolic extracts from RPMI 88.66 but not other B lymphoma exhibit altered levels of cytochrome c-dependent caspase activation. Taken together, our results show that: (1) death receptor expression does not correlate with sensitivity to apoptosis; (2) the very low ratio of DFF40 vs DFF45 is unlikely to explain by itself the lack of DNA fragmentation observed in certain B cell lines; and (3) a defective cytochrome c-dependent caspase activation might account at least in part for the insensitivity of certain Burkitt's lymphoma (RPMI 88.66) to apoptosis. Thus it seems that resistance of Burkitt's lymphoma to apoptosis is not governed by a general mechanism, but is rather multifactorial and differs from one cell line to another.