Maturation of oligodendrocytes is more sensitive to TNFα than is survival of precursors and immature oligodendrocytes
Maturation of oligodendrocytes is more sensitive to TNFα than is survival of precursors and immature oligodendrocytes
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DOI：
10.1016/s0165-5728(99)00045-4
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发表时间：
1999-06-01
影响因子：
3.3
通讯作者：
Zhang, H
中科院分区：
文献类型：
--
作者：
Cammer, W;Zhang, H
肿瘤坏死因子α是最近在多发性硬化症斑块中发现的一种高水平的细胞因子。本研究提出了以下问题：肿瘤坏死因子α是否会影响不同成熟阶段的少突胶质细胞，以及在随后的分化过程中，与肿瘤坏死因子α瞬时孵育的影响是否会持续。原代培养的胶质细胞用1000U/ml的肿瘤坏死因子α处理48h，从体外培养的第1、2、6、8和10天开始，并在体外生长至多3周。在经肿瘤坏死因子α处理的培养物中，O4+/MBP+细胞在第二周变得明显不足。此外，在对照培养中，O4阳性细胞的形态随着时间的推移而变得更加复杂，而在经肿瘤坏死因子α处理的培养中，较少的细胞发育成具有片状或四个突起的细胞。在经肿瘤坏死因子α处理的培养物中，O4阳性细胞的数量在第2周和第3周增加了约4倍，但MBP阳性细胞的数量没有增加，而且显著低于对照培养物中MBP阳性细胞的数量。治疗后1至14天，肿瘤坏死因子α的作用明显，提示有长期影响，并可在不同的成熟阶段启动。未来对肿瘤坏死因子α抑制少突胶质细胞分化的假设机制的测试应该会影响我们对成熟中枢神经系统髓鞘再分化的明显限制的理解。(C)1999 Elsevier Science B.V.保留所有权利。
TNF alpha is a cytokine recently found at high levels in multiple sclerosis plaques. The present study addressed the questions whether TNF alpha might affect oligodendrocytes at various stages of maturation and whether the effects of transient incubation with TNF alpha would last during subsequent differentiation. Primary glial-cell cultures were treated with 1000 U/ml of TNF alpha for 48 h, beginning on days 1, 2, 6, 8 and 10 days in vitro, and allowed to grow for up to 3 weeks (total) in vitro. A significant deficit of O4 + /MBP + cells in the TNF alpha-treated cultures became obvious during the second week. Moreover, the morphology of the O4-positive cells became more complex with time in the control cultures, whereas fewer cells in TNF alpha-treated cultures developed into cells with sheets of membrane or > four processes. In TNF alpha-treated cultures, the numbers of O4-positive cells increased by about four-fold during weeks 2 and 3, but the numbers of MBP-positive cells did not and were significantly lower than the numbers of MBP-positive cells in control cultures. The effects of TNF alpha were apparent 1 to 14 days after treatment, suggesting long-term influences, and could be initiated at diverse stages of maturation. Future testing of hypothetical mechanisms by which TNF alpha may inhibit oligodendrocyte differentiation should impact on our understanding of the apparent limitations on remyelination in the mature CNS. (C) 1999 Elsevier Science B.V. All rights reserved.