基于补体研究证据的淀粉体的功能作用

S.K Singhrao , B.P Morgan , J.W Neal , G.R Newman
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引用次数: 44

摘要

关于正常衰老的大脑和中枢神经系统在各种神经系统条件下产生淀粉体(CA)的理论很少。在CA中发现了来自神经元和少突胶质细胞的蛋白质,为了了解它们的来源,我们对阿尔茨海默病(AD)、多发性硬化症(MS)和皮克病(PD)患者的脑组织进行了补体活性检测。所有CA对经典途径特异性组分、活化产物C3d和末端补体复合体(TCC)、C3转化酶调节剂膜辅助因子蛋白(MCP)、液相调节剂s蛋白和簇蛋白的抗血清均呈免疫阳性。CA对替代补体途径蛋白、补体调节因子、衰减加速因子(DAF)和CD59均呈免疫阴性。从同一组织中分离的溶解CA的Western免疫印迹显示MCP有一周的频带,而TCC更容易通过免疫沉淀显示。CA周围的丝状条纹,可能是星形细胞起源,补体因子免疫阳性。CA由惰性粘多糖基质包裹泛素化蛋白组成,由神经元、髓磷脂和少突胶质细胞的死亡和损伤引起。因此,CA的功能可能是阻止淋巴细胞和小胶质细胞对这些免疫原性蛋白的识别,从而保护中枢神经系统免受进一步损伤。
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A functional role for corpora amylacea based on evidence from complement studies

Few theories have been advanced for the production of corpora amylacea (CA) by the normal ageing brain and by the CNS under various neurological conditions. Proteins derived from neurons and oligodendrocytes are found in CA and to understand their origins brain tissue from patients with Alzheimer's disease (AD), multiple sclerosis (MS) and Pick's disease (PD) were tested for complement activity. All CA were immunopositive for antisera to classical pathway-specific components, the activation products C3d and the terminal complement complex (TCC), the C3 convertase regulator membrane cofactor protein (MCP) and the fluid phase regulators S-protein and clusterin. CA were immunonegative for the alternative complement pathway proteins and the complement regulators, decay accelerating factor (DAF) and CD59. Western immunoblotting of isolated solubilized CA from the same tissues demonstrated a week band for MCP but TCC was more easily shown by immunoprecipitaton. A filamentous fringe around CA, probably of astrocytic origin, was also immunopositive for complement factors. CA consist of an inert mucopolysaccharide matrix encasing ubiquitinated proteins, resulting from death of and damage to neurons, myelin and oligodendrocytes. A function of CA, therefore, could be to prevent the recognition of these immunogenic proteins by lymphocytes and microglia and thus protect the CNS from further injury.

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