Department of Human Anatomy, Weifang Medical University, Weifang 261053, China.
Int J Biochem Cell Biol. 2013 Aug;45(8):1911-20. doi: 10.1016/j.biocel.2013.06.005. Epub 2013 Jun 17.
Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease.
氧化和免疫攻击来自环境或小胶质细胞，已经涉及帕金森病中多巴胺能神经元的丧失。在帕金森病的过程中，免疫球蛋白 IgG 作为一种重要的免疫分子的作用尚不清楚。有证据表明，除了传统上公认的来源 B 淋巴细胞之外，IgG 还可以由神经元产生，但神经元中 IgG 的功能知之甚少。在这项研究中，在人类和大鼠中脑的多巴胺能神经元中广泛表达了神经元衍生的 IgG。通过体外帕金森病模型，我们发现神经元衍生的 IgG 可以改善多巴胺能神经元的存活并减少 6-羟多巴胺毒性诱导的细胞凋亡，还可以抑制 6-羟多巴胺引发的小胶质细胞中 NO 的释放。通过 FcγR I 和 TLR4 途径，神经元衍生的 IgG 将小胶质细胞中 TNF-α和 IL-10 的表达上调至生理水平的保护水平，并且 IgG 阻断可以减轻小胶质细胞的激活。所有这些数据表明，神经元衍生的 IgG 通过适当激活小胶质细胞可能发挥自身保护功能，并且 IgG 可能参与维持中枢神经系统的免疫平衡，并在帕金森病等病理条件下作为一个活跃因素。
