Walker D G, Yasuhara O, Patston P A, McGeer E G, McGeer P L
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.
Brain Res. 1995 Mar 27;675(1-2):75-82. doi: 10.1016/0006-8993(95)00041-n.
C1 inhibitor was identified in human brain tissue by Western blotting and by immunohistochemistry using multiple antibodies to the native protein. The presence of C1 inhibitor mRNA was identified by reverse transcriptase-polymerase chain reaction analysis of brain mRNA extracts. The mRNA was also detected in cultured postmortem human microglia and in the IMR-32 human neuroblastoma cell line. Immunohistochemically, the native protein was detected in residual serum of capillaries and pyramidal neurons of both control and Alzheimer disease cases, as well as in occasional senile plaques of Alzheimer tissue. The reacted protein was detected on dystrophic neurites and neuropil threads in Alzheimer tissue by 4C3 monoclonal antibody, which recognizes a neoepitope following suicide inhibition. These data indicate that C1 inhibitor, a regulatory molecule controlling multiple inflammatory proteolytic cascades, is produced in normal brain. In Alzheimer disease, C1 inhibitor undergoes a prominent reaction in abnormal neuronal processes, such as dystrophic neurites and neuropil threads.
通过蛋白质免疫印迹法以及使用针对天然蛋白的多种抗体进行免疫组织化学，在人脑组织中鉴定出了C1抑制剂。通过对脑mRNA提取物进行逆转录聚合酶链反应分析，确定了C1抑制剂mRNA的存在。在培养的死后人类小胶质细胞和IMR-32人神经母细胞瘤细胞系中也检测到了该mRNA。免疫组织化学结果显示，在对照和阿尔茨海默病病例的毛细血管残余血清和锥体神经元中均检测到了天然蛋白，在阿尔茨海默病组织的偶尔出现的老年斑中也检测到了。通过识别自杀抑制后新表位的4C3单克隆抗体，在阿尔茨海默病组织的营养不良性神经突和神经毡丝上检测到了反应蛋白。这些数据表明，C1抑制剂作为一种控制多种炎症蛋白水解级联反应的调节分子，在正常大脑中产生。在阿尔茨海默病中，C1抑制剂在异常神经元过程（如营养不良性神经突和神经毡丝）中发生显著反应。
