Complement is activated in progressive multiple sclerosis cortical grey matter lesions.
Complement is activated in progressive multiple sclerosis cortical grey matter lesions.
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DOI：
10.1186/s12974-016-0611-x
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发表时间：
2016-06-22
影响因子：
9.3
通讯作者：
Howell OW
中科院分区：
文献类型：
--
作者：
Watkins LM;Neal JW;Loveless S;Michailidou I;Ramaglia V;Rees MI;Reynolds R;Robertson NP;Morgan BP;Howell OW
多发性硬化症（MS）的症状是由脑和脊髓中的髓鞘和神经细胞受损引起的。炎症与神经退行性变密切相关，并且神经退行性变的积累是进行性MS中神经功能障碍增加的基础。因此，确定MS灰质中起作用的病理机制是我们理解疾病进展的关键。我们分析了补体的表达和激活的免疫细胞化学和原位杂交冷冻或福尔马林固定石蜡包埋死后组织块从22个进行性MS的情况下，并进行了比较，炎症性中枢神经系统疾病和非神经系统疾病的控制。C1 qA的转录本的表达在神经元和激活片段和调理素C3 b标记的神经元和神经胶质细胞在MS皮质和深灰质。经典补体途径蛋白C1 q和替代补体途径激活片段Bb的免疫染色阳性细胞的密度显着增加皮质灰质病变相比，控制灰质。在皮质病变中，膜攻击复合物免疫染色的细胞数量升高，表明补体激活完成。MS和对照组之间经典（C1抑制剂）和替代（H因子）途径调节剂阳性细胞的数量没有变化，而MS皮质中携带过敏毒素受体的小胶质细胞被发现与皮质神经元密切相关。补体免疫阳性神经元显示改变的核形态，表明细胞应激/损伤，支持我们的发现，在皮质灰质病变的显着神经变性。补体激活的MS皮质灰质病变的补体受体阳性小胶质细胞数量增加的地区，并表明，补体过度激活可能导致恶化的病理基础MS的不可逆进展。这篇文章的在线版本（doi：10.1186/s12974-016-0611-x）包含补充材料，这是提供给授权用户。
The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the irreversible progression of MS. The online version of this article (doi:10.1186/s12974-016-0611-x) contains supplementary material, which is available to authorized users.