Selmaj K, Raine C S, Farooq M, Norton W T, Brosnan C F
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
J Immunol. 1991 Sep 1;147(5):1522-9.
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.
重组人细胞因子对从成年牛脑培养的神经胶质细胞的细胞毒性作用进行了测试。淋巴毒素（LT）和肿瘤坏死因子（TNF）以时间和剂量依赖性方式诱导少突胶质细胞损伤。所测试的其他细胞因子，γ干扰素（IFN-γ）、白细胞介素-6（IL-6）和白细胞介素-2（IL-2），在72小时的观察期内对培养的少突胶质细胞没有影响。没有一种细胞因子对从相同来源培养的星形胶质细胞造成损伤。与TNF相比，LT对少突胶质细胞表现出更强的细胞毒性；在更低的活性单位下更早（24小时）就观察到细胞毒性变化。形态学研究表明，LT介导的效应与细胞突起的早期回缩、F-肌动蛋白解聚以及随后的核变性有关。通过51Cr释放测量未发现早期细胞质膜损伤，并且电子显微镜研究显示核崩解，这表明LT诱发的少突胶质细胞损伤存在凋亡机制，DNA完整性检测支持了这一点。这些结果表明，LT对少突胶质细胞具有强大的细胞毒性活性，并且该过程涉及的主要机制是DNA片段化。
