Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin.
Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin.
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DOI：
10.4049/jimmunol.147.5.1522
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发表时间：
1991-09
影响因子：
4.4
通讯作者：
K. Selmaj;C. Raine;M. Farooq;W. T. Norton;C. Brosnan
中科院分区：
文献类型：
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作者：
K. Selmaj;C. Raine;M. Farooq;W. T. Norton;C. Brosnan
在成熟牛脑培养的神经胶质细胞上测试了重组人细胞因子的细胞毒作用。淋巴毒素 (LT) 和 TNF 以时间和剂量依赖性方式诱导少突胶质细胞损伤。测试的其他细胞因子，IFN-γ、IL-6 和 IL-2，在 72 小时的观察期内不影响培养物中的少突胶质细胞。没有一种细胞因子会损伤同一来源培养的星形胶质细胞。 LT 对少突胶质细胞表现出比 TNF 更强的细胞毒性；细胞毒性变化较早（24小时）且在较低的活性单位下被注意到。形态学研究表明，LT 介导的效应与细胞过程的早期回缩、F-肌动蛋白的解聚以及随后的核变性有关。通过 51Cr 释放和电子显微镜研究测量，缺乏早期细胞质膜损伤，证明核崩解表明 LT 诱发少突胶质细胞损伤的凋亡机制，这一点得到了 DNA 完整性测定的支持。这些结果表明，LT 对少突胶质细胞具有有效的细胞毒活性，并且该过程中涉及的主要机制是 DNA 片段化。
The cytotoxic effect of recombinant human cytokines was tested on glial cells cultured from mature bovine brain. Lymphotoxin (LT) and TNF induced injury to oligodendrocytes in a time and dose-dependent fashion. The other cytokines tested, IFN-gamma, IL-6, and IL-2, did not affect oligodendrocytes in culture over a 72-h observation period. None of the cytokines injured astrocytes cultured from the same source. LT showed a much more potent cytotoxicity than TNF toward oligodendrocytes; cytotoxic changes were noted earlier (24 h) and at lower units of activity. Morphologic studies showed that the LT-mediated effects were associated with early retraction of cell processes, depolymerization of F-actin and subsequent nuclear degeneration. Lack of early cytoplasmic membrane injury as measured by 51Cr release and electron microscope studies demonstrating nuclear disintegration suggested an apoptotic mechanism of oligodendrocyte injury evoked by LT, which was supported by DNA integrity assay. These results demonstrate that LT possesses potent cytotoxic activity against oligodendrocytes and that the major mechanism involved in this process is DNA fragmentation.