Weinmann Oliver, Schnell Lisa, Ghosh Arko, Montani Laura, Wiessner Christoph, Wannier Thierry, Rouiller Eric, Mir Anis, Schwab Martin E
Brain Research Institute, University of Zurich and Department Biology, ETH Zurich, Winterthurerstr. 190 8057 Zurich, Switzerland.
Mol Cell Neurosci. 2006 May-Jun;32(1-2):161-73. doi: 10.1016/j.mcn.2006.03.007. Epub 2006 May 11.
Neutralizing antibodies against the neurite growth inhibitory protein Nogo-A are known to induce regeneration, enhance compensatory growth, and enhance functional recovery. In intact adult rats and monkeys or spinal cord injured adult rats, antibodies reached the entire spinal cord and brain through the CSF circulation from intraventricular or intrathecal infusion sites. In the tissue, anti-Nogo antibodies were found inside Nogo-A expressing oligodendrocytes and neurons. Intracellularly, anti-Nogo-A antibodies were colocalized with endogenous Nogo-A in large organels, some of which containing the lysosomal marker cathepsin-D. This suggests antibody-induced internalization of cell surface Nogo-A. Total Nogo-A tissue levels in spinal cord were decreased in intact adult rats following 7 days of antibody infusion. This mechanism was confirmed in vitro; cultured oligodendrocytes and neurons had lower Nogo-A contents in the presence of anti-Nogo-A antibodies. These results demonstrate that antibodies against a CNS cell surface protein reach their antigen through the CSF and can induce its downregulation.
已知针对神经突生长抑制蛋白Nogo - A的中和抗体可诱导再生、增强代偿性生长并促进功能恢复。在完整的成年大鼠和猴子或脊髓损伤的成年大鼠中，抗体通过脑脊液循环从脑室内或鞘内注射部位到达整个脊髓和大脑。在组织中，抗Nogo抗体在表达Nogo - A的少突胶质细胞和神经元内部被发现。在细胞内，抗Nogo - A抗体与内源性Nogo - A在大型细胞器中共定位，其中一些细胞器含有溶酶体标记物组织蛋白酶D。这表明抗体诱导细胞表面Nogo - A的内化。在成年大鼠完整脊髓中，抗体注射7天后，脊髓中Nogo - A的总组织水平降低。这一机制在体外得到证实；在存在抗Nogo - A抗体的情况下，培养的少突胶质细胞和神经元中的Nogo - A含量较低。这些结果表明，针对中枢神经系统细胞表面蛋白的抗体可通过脑脊液到达其抗原并诱导其下调。
