Hosokawa Masato, Klegeris Andis, Maguire John, McGeer Patrick L
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.
Glia. 2003 Jun;42(4):417-23. doi: 10.1002/glia.10234.
Neurons, astrocytes, microglia, and endothelial cells are capable of synthesizing most, if not all, of the complement proteins. Little is known, however, about the capacity of oligodendroglial cells to generate complement components. This study evaluated expression of complement mRNAs and their protein products by human oligodendrocytes. Cells were isolated and cultured from white matter of seven adult cases that had undergone surgical temporal lobe resection for epilepsy. Oligodendroglial cultures were characterized by the expression of such cell type-specific mRNAs as myelin proteolipid protein (PLP), oligodendrocyte-specific protein (OSP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and were further characterized by immunostaining for such differentiation markers as myelin basic protein (MBP), PLP, CNPase, and O4. RT-PCR analysis showed that the oligodendroglial cells expressed detectable levels of complement mRNAs for the C1q B-chain, C1r, C1s, C2, C3, C4, C5, C6, C7, C8 gamma subunit, and C9. Immunostaining was positive for C1q, C1s, C2, C3, C4, C5, C6, C7, C8, and C9. Double immunostaining for the oligodendrocyte marker O4 and the complement protein C3 demonstrated that all O4-positive cells were also positive for C3, indicating constitutive C3 expression. These results indicate that oligodendroglial cells may be a source of complement proteins in human brain and thus could contribute to the pathogenesis of several neurodegenerative and inflammatory diseases of the CNS, such as Alzheimer's disease, multiple sclerosis, and progressive supranuclear palsy, where complement-activated oligodendrocytes are abundant.
神经元、星形胶质细胞、小胶质细胞和内皮细胞能够合成大部分(即便不是全部)补体蛋白。然而,关于少突胶质细胞产生补体成分的能力却知之甚少。本研究评估了人少突胶质细胞中补体mRNA及其蛋白产物的表达。从7例因癫痫接受颞叶手术切除的成人病例的白质中分离并培养细胞。少突胶质细胞培养物通过髓磷脂蛋白脂蛋白(PLP)、少突胶质细胞特异性蛋白(OSP)和2',3'-环核苷酸3'-磷酸二酯酶(CNPase)等细胞类型特异性mRNA的表达进行表征,并通过对髓磷脂碱性蛋白(MBP)、PLP、CNPase和O4等分化标志物的免疫染色进一步表征。逆转录聚合酶链反应(RT-PCR)分析表明,少突胶质细胞表达了可检测水平的C1q B链、C1r、C1s、C2、C3、C4、C5、C6、C7、C8γ亚基和C9的补体mRNA。免疫染色显示C1q、C1s、C2、C3、C4、C5、C6、C7、C8和C9呈阳性。少突胶质细胞标志物O4和补体蛋白C3的双重免疫染色表明,所有O4阳性细胞C3也呈阳性,表明C3组成性表达。这些结果表明,少突胶质细胞可能是人类大脑中补体蛋白的一个来源,因此可能在中枢神经系统的几种神经退行性和炎症性疾病(如阿尔茨海默病、多发性硬化症和进行性核上性麻痹)的发病机制中起作用,在这些疾病中,补体激活的少突胶质细胞大量存在。