Robaye B, Mosselmans R, Fiers W, Dumont J E, Galand P
Institut de Recherche Interdisciplinaire en Humaine et Nucléaire (IIRIBHN), Faculté de Médecine, Free University of Brussels, Belgium.
Am J Pathol. 1991 Feb;138(2):447-53.
Tumor necrosis factor (TNF) is cytotoxic for many tumoral cell lines, whereas normal cells generally are considered resistant to this action. This study shows that this cytokine causes massive death of bovine endothelial cells in primary culture in a concentration- and time-dependent manner. Dying cells exhibit all the ultrastructural changes and the inter-nucleosome cleavage of DNA associated with apoptosis or 'programmed cell death.' This is the first report clearly showing a direct toxicity of TNF on endothelial cells and demonstrating that this results from the induction of the program of apoptotic death. Our observation raises the possibility that hemorrhagic necrosis in vivo, after treatment with TNF, might involve a direct cytocidal action on endothelial cells of the tumor neovasculature.
肿瘤坏死因子（TNF）对许多肿瘤细胞系具有细胞毒性，而正常细胞通常被认为对这种作用具有抗性。本研究表明，这种细胞因子以浓度和时间依赖性方式导致原代培养的牛内皮细胞大量死亡。死亡细胞表现出与凋亡或“程序性细胞死亡”相关的所有超微结构变化以及DNA的核小体间切割。这是第一份明确显示TNF对内皮细胞具有直接毒性并证明这是由凋亡死亡程序的诱导所致的报告。我们的观察结果提出了一种可能性，即TNF治疗后体内的出血性坏死可能涉及对肿瘤新生血管内皮细胞的直接杀细胞作用。
