Yang Zhao, Zhong Shanchuan, Liu Yongping, Shen Hanchao, Yuan Bangqing
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.
J Neuroimmunol. 2015 Jan 15;278:232-8. doi: 10.1016/j.jneuroim.2014.11.010. Epub 2014 Nov 14.
Microglia mediated neuroinflammation plays a crucial role in intracerebral hemorrhage (ICH). Therefore, the negative feedback immune mechanism to keep microglia homeostasis and inhibit the related inflammatory injury is important. Scavenger receptor A (SRA), a pattern recognition molecule, is a physiologic negative regulator of immune consequences. However, its role in microglia mediated immune response has not been well defined. In this study, we detected SRA expression and inflammatory response of microglia treated with erythrocyte lysate in vitro, and observed the cerebral water content and neurological deficit of ICH mice in vivo. We found that SRA was highly expressed in erythrocyte lysate treated microglia. Interestingly, genetic SRA ablation increased microglia activation and cytokine production, and sensitized mice to ICH induced neuron injury. In addition, we adoptive transferred microglia (WT) into ICH mice (SRA-/-), and found that the ICH-induced inflammation injury was effectively ameliorated. Therefore, the results demonstrated that SRA could attenuate microglia mediated inflammation injury in ICH. In addition, SRA mediated negative feedback mechanism in neuroimmune homeostasis might provide a novel therapeutical strategy for ICH. Scavenger receptor SRA restrains T cell activation and protects against concanavalin A-induced hepatic injury.
小胶质细胞介导的神经炎症在脑出血(ICH)中起关键作用。因此,维持小胶质细胞稳态并抑制相关炎症损伤的负反馈免疫机制很重要。清道夫受体A(SRA)作为一种模式识别分子,是免疫反应的生理负调节因子。然而,其在小胶质细胞介导的免疫反应中的作用尚未明确界定。在本研究中,我们检测了体外经红细胞裂解物处理的小胶质细胞的SRA表达和炎症反应,并在体内观察了ICH小鼠的脑含水量和神经功能缺损。我们发现SRA在经红细胞裂解物处理的小胶质细胞中高表达。有趣的是,基因敲除SRA会增加小胶质细胞的活化和细胞因子产生,并使小鼠对ICH诱导的神经元损伤更敏感。此外,我们将小胶质细胞(野生型)过继转移到ICH小鼠(SRA基因敲除型)体内,发现ICH诱导的炎症损伤得到有效改善。因此,结果表明SRA可减轻ICH中小胶质细胞介导的炎症损伤。此外,SRA在神经免疫稳态中介导的负反馈机制可能为ICH提供一种新的治疗策略。清道夫受体SRA可抑制T细胞活化并预防伴刀豆球蛋白A诱导的肝损伤。