Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain
Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain
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DOI：
10.1084/jem.184.4.1513
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发表时间：
1996-10-01
影响因子：
15.3
通讯作者：
Husar, W
中科院分区：
文献类型：
--
作者：
Dowling, P;Shang, GF;Husar, W
使用免疫组织化学方法来寻找参与多发性硬化症 (MS) 白质脑损伤的 Fas 受体/Fas 配体系统。我们发现在两个急性病变和 16 个慢性 MS 病变中的 12 个中存在大量带有 Fas 配体 (Fas-L) 的细胞，而在非炎症对照中则很少有阳性细胞。然而，来自与炎症和白质疾病相关的非 MS 神经病理状况的 6 个大脑中，有 4 个的 Fas-L 也呈阳性。细胞特异性标记物的双重染色显示，慢性 MS 病变中配体阳性细胞的模式很复杂，由几种不同的细胞类型组成，这些细胞类型主要是常驻神经胶质细胞，并覆盖有少量巨噬细胞。还评估了 MS 组织中的 Fas/APO 1 (CD95) 受体表达，发现该受体显着上调。此外，在许多对照大脑中，Fas受体被诱导，但程度较小。观察到TUNEL阳性死亡细胞存在于多发性硬化症病变中，并与Fas-L表现出良好的共定位，表明Fas死亡系统可能有助于斑块发病机制，并可能导致开发一类新的多发性硬化症治疗药物。
Immunohistochemical methods were used to search for Fas receptor/Fas ligand system involvement in multiple sclerosis (MS) white matter brain lesions. We found large numbers of Fas Ligand (Fas-L)-bearing cells present in two acute lesions and 12 of 16 chronic MS lesions, and very few positive cells in non-inflammatory controls. Four of six brains from non-MS neuropathologic conditions associated with inflammation and white matter disease were, however, also positive for Fas-L, Double staining with cell-specific markers revealed that the pattern of ligand-positive cells in chronic MS lesions was complex and composed of several different cell types which were primarily resident glial cells with a small overlay of macrophages. Fas/APO 1 (CD95) receptor expression in MS tissue was also evaluated and marked upregulation of the receptor was found. In addition, Fas receptor was induced, but to a lesser extent, in numerous control brains, The observations that TUNEL-positive dying cells were present in MS lesions and showed excellent co-localization with Fas-L, indicate that the Fas death system may contribute to plaque pathogenesis and could lead to the development of a new category of therapeutic agents for MS.