TNF-α和其他细胞毒剂诱导L929细胞死亡的模式,Cytokine

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TNF-α和其他细胞毒剂诱导L929细胞死亡的模式
Cytokine ( IF 3.7 ) Pub Date : 1999-10-01 , DOI: 10.1006/cyto.1998.0492
D T Humphreys ₁ , M R Wilson

Affiliation

最近的研究不同程度地报道了肿瘤坏死因子 α (TNF-α) 在 L929 细胞中诱导坏死或凋亡。进行这项研究是为了更好地表征该药剂在 L929 细胞中诱导的死亡模式。我们确定了暴露于 TNF-α 和其他细胞毒性剂对细胞大小和形态、细胞膜通透性、细胞表面磷脂酰丝氨酸的暴露、核形态和 DNA 片段化的影响。我们的结果表明，单独用 TNF-α 处理的 L929 细胞显示出细胞核变化和非典型细胞凋亡的 DNA 片段化模式。相比之下，我们的结果表明，当用放线菌素 D 增强时，TNF-α 在 L929 细胞中诱导经典细胞凋亡。我们还提供了第一份报告，在 L929 细胞中，staurosporine 诱导经典细胞凋亡，而秋水仙碱诱导一种缺乏核小体间 DNA 断裂的细胞凋亡形式。先前对 L929 细胞中 TNF-α 诱导的死亡的研究依赖于仅测量一两个参数来定义死亡模式。总体而言，我们的结果表明，在未来关于 TNF-α 对 L929 细胞影响的细胞或生化研究中，谨慎地使用多参数方法来表征每种情况下的死亡模式，如此处所做的。

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MODES OF L929 CELL DEATH INDUCED BY TNF-α AND OTHER CYTOTOXIC AGENTS

Recent studies have variably reported that tumour necrosis factor alpha (TNF-alpha) induces either necrosis or apoptosis in L929 cells. This study was undertaken to better characterize the mode of death induced in L929 cells by this agent. We determined the effects of exposure to TNF-alpha and other cytotoxic agents on cell size and morphology, cell membrane permeability, exposure of phosphatidylserine at the cell surface, nuclear morphology and fragmentation of DNA. Our results suggest that L929 cells treated with TNF-alpha alone show nuclear changes and a pattern of DNA fragmentation that are atypical of apoptosis. In contrast, our results demonstrate that, when augmented with actinomycin D, TNF-alpha induces classical apoptosis in L929 cells. We also provide the first report that, in L929 cells, staurosporine induces classical apoptosis and colchicine induces a form of apoptosis lacking internucleosomal DNA fragmentation. Previous studies of TNF-alpha-induced death in L929 cells relied on measurements of only one or two parameters to define the mode of death. Overall, our results suggest that in future cellular or biochemical studies of the effects of TNF-alpha on L929 cells it will be prudent to characterize the mode of death in each case using a multi-parameter approach, as done here.

更新日期：1999-10-01

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