Complement activation in multiple sclerosis plaques: an immunohistochemical analysis.
Complement activation in multiple sclerosis plaques: an immunohistochemical analysis.
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DOI：
10.1186/2051-5960-2-53
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发表时间：
2014-05-09
影响因子：
7.1
通讯作者：
Morgan BP
中科院分区：
文献类型：
--
作者：
Ingram G;Loveless S;Howell OW;Hakobyan S;Dancey B;Harris CL;Robertson NP;Neal JW;Morgan BP
炎症和补体激活与多发性硬化的病理学密切相关;然而，它们参与特定病理过程（如轴突损伤、髓鞘丢失和疾病进展）的程度和性质仍不确定。本研究旨在澄清这些问题。我们描述了一个详细的免疫组化研究，本地化的战略选择的一套补体蛋白，激活产品和监管机构在大脑和脊髓组织的17例进行性多发性硬化症和16个控制捐助者，包括9个中枢神经系统疾病。检查活动性、慢性活动性和慢性非活动性多发性硬化斑块（共35个）和非斑块区域。多发性硬化斑块的补体蛋白（C3、因子B、C1 q）、活化产物（C3 B、iC 3 B、C4 d、末端补体复合物）和调节因子（因子H、C1抑制剂、丛生蛋白）始终呈阳性，表明尽管没有其他持续炎症的证据，但仍存在持续的局部补体合成、活化和调节。补体染色在斑块和斑块周围最明显，但也存在于正常外观的白色物质和皮质区，其程度大于对照组织。C1 q染色存在于所有斑块中，表明经典途径的主导作用。补体成分的细胞染色主要局限于反应性星形胶质细胞，通常邻近于与补体调理髓鞘和受损轴突紧密并列的小胶质细胞簇。这些发现表明补体参与多发性硬化症的普遍性，表明补体对细胞，轴突和髓鞘损伤的致病作用，并为多发性硬化症的监测和治疗提供靶向补体的理由。本文的在线版本（doi：10.1186/2051-5960-2-53）包含补充材料，可供授权用户使用。
Inflammation and complement activation are firmly implicated in the pathology of multiple sclerosis; however, the extent and nature of their involvement in specific pathological processes such as axonal damage, myelin loss and disease progression remains uncertain. This study aims to bring clarity to these questions. We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive multiple sclerosis and 16 control donors, including 9 with central nervous system disease. Active, chronic active and chronic inactive multiple sclerosis plaques (35 in total) and non-plaque areas were examined. Multiple sclerosis plaques were consistently positive for complement proteins (C3, factor B, C1q), activation products (C3b, iC3b, C4d, terminal complement complex) and regulators (factor H, C1-inhibitor, clusterin), suggesting continuing local complement synthesis, activation and regulation despite the absence of other evidence of ongoing inflammation. Complement staining was most apparent in plaque and peri-plaque but also present in normal appearing white matter and cortical areas to a greater extent than in control tissue. C1q staining was present in all plaques suggesting a dominant role for the classical pathway. Cellular staining for complement components was largely restricted to reactive astrocytes, often adjacent to clusters of microglia in close apposition to complement opsonised myelin and damaged axons. The findings demonstrate the ubiquity of complement involvement in multiple sclerosis, suggest a pathogenic role for complement contributing to cell, axon and myelin damage and make the case for targeting complement for multiple sclerosis monitoring and therapy. The online version of this article (doi:10.1186/2051-5960-2-53) contains supplementary material, which is available to authorized users.
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DOI：
10.1177/1352458512438238
发表时间：
2012-10
期刊：
Multiple sclerosis (Houndmills, Basingstoke, England)
影响因子：
--
作者：
Ingram G;Hakobyan S;Hirst CL;Harris CL;Loveless S;Mitchell JP;Pickersgill TP;Robertson NP;Morgan BP
通讯作者：
Morgan BP
影响因子：
2.9
作者：
LUMSDEN, CE
通讯作者：
LUMSDEN, CE
影响因子：
4.4
作者：
Kira, Jun-ichi
通讯作者：
Kira, Jun-ichi
影响因子：
11.2
作者：
Breij, Esther C. W.;Brink, Bianca P.;Boe, Lars
通讯作者：
Boe, Lars
影响因子：
15.9
作者：
Qin, YF;Duquette, P;Antel, J
通讯作者：
Antel, J