Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
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DOI：
10.4049/jimmunol.141.8.2629
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发表时间：
1988-10
影响因子：
4.4
通讯作者：
S. Laster;J. G. Wood;L. Gooding
中科院分区：
文献类型：
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作者：
S. Laster;J. G. Wood;L. Gooding
TNF是由活化的巨噬细胞和单核细胞分泌的蛋白质毒素。虽然TNF的细胞毒活性已被充分证明，但TNF诱导的裂解机制尚未完全了解。本研究的目的是确定TNF是否引起细胞死亡的经典形式之一，即，细胞凋亡，其特征在于细胞核解体和细胞质“沸腾”，或坏死，其特征在于形成“气球样”质膜和缺乏细胞核解体。因此，为了区分凋亡和坏死，我们使用延时视频显微镜观察了几种TNF敏感的靶细胞系的死亡，同时分别测量了胞质和核室中Na 2（51）CrO 4和[3 H]TdR的释放。作为目标，我们选择了两个自发敏感的细胞系，F17和L-M，和一个耐药细胞系，C3 HA，这是通过用放线菌酮处理或感染腺病毒-SV 40杂合病毒Ad 2 + ND 2致敏。我们发现观察到的细胞死亡类型取决于被测试的细胞。例如，在F17细胞中，我们发现TNF处理诱导了经典形式的凋亡。相反，TNF诱导L-M细胞的细胞死亡的坏死形式，类似于由抗体和C.最后，我们发现致敏的C3 HA细胞表现出一种新的溶细胞表型，类似于凋亡，但不包括DNA片段化。这些结果强调了TNF诱导的细胞毒性反应的复杂性。
TNF is a protein toxin which is secreted by activated macrophages and monocytes. Although the cytotoxic activity of TNF has been well documented, the mechanism of TNF-induced lysis is not well understood. The goal of this investigation was to determine whether TNF caused one of the classic forms of cell death, i.e., apoptosis, which is characterized by nuclear disintegration and cytoplasmic "boiling," or necrosis, which is characterized by the formation of a "balloon-like" plasma membrane and a lack of nuclear disintegration. Therefore, to distinguish apoptosis from necrosis, we have used time-lapse video microscopy to observe the death of several TNF-sensitive target cell lines while measuring the release of Na2(51)CrO4 and [3H]TdR from cytoplasmic and nuclear compartments, respectively. As targets we selected two spontaneously sensitive cell lines, F17 and L-M, and one resistant cell line, C3HA, which was sensitized by treatment with cycloheximide or by infection with the adeno-SV40 hybrid virus Ad2+ND2. We find that the type of cell death observed depends on the cell being tested. For example, in F17 cells we found that TNF treatment induced a classical form of apoptosis. In contrast, TNF induced a necrotic form of cell death in L-M cells, similar to the lysis induced by antibody and C. Finally, we found that sensitized C3HA cells displayed a novel cytolytic phenotype which resembled apoptosis but did not include DNA fragmentation. These results emphasize the complex nature of the TNF-induced cytotoxic response.