严重急性呼吸综合征冠状病毒S蛋白启动急性肺损伤的可能机制  

The possible mechanism of the acute lung injury induced by S protein of SARS-CoV

作　　者：要国华[1] 杨新艳[1] 徐军[1] 

机构地区：[1]广州医学院附属第一医院广州呼吸疾病研究所,广东广州510120

出　　处：《医学研究生学报》2005年第8期677-681,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金资助项目(批准号:30340029);广东省教育厅非典专项经费;广东省非典攻关病原学专项基金资助项目(批准号:303001010)

摘　　要：目的:研究严重急性呼吸综合征(SARS)冠状病毒(CoV)S蛋白作用于呼吸道上皮及免疫细胞后对趋化因子IP-10和其他细胞因子生成的影响。方法:通过昆虫-杆状病毒表达系统表达SARS-CoV的S蛋白,并经镍亲和磁珠纯化,将重组的S蛋白分别作用于人支气管上皮细胞16HBE、外周血单个核细胞和单核细胞、肺泡单核-巨噬细胞,观察其形态学变化,并检测IP-10和其他细胞因子的变化。结果:基础状态下16HBE并不生成IP-10,S蛋白作用于人支气管上皮细胞16HBE,引起部分细胞变圆、空泡形成并裂解,12h后即可见IP-10生成达(79.97±13.81)pg/ml,呈显著量效关系。但对其他参与免疫反应的Th1/Th2细胞因子及趋化因子影响不明显。S蛋白并不诱导外周血单核细胞和单个核细胞(主要为淋巴细胞)合成释放IP-10。比较而言,干扰素-γ(IFN-γ)不仅能诱导16HBE,而能诱导免疫细胞生成IP-10。结论:①SARS-CoV可通过其S蛋白早期诱导肺上皮细胞合成释放IP-10,从而启动免疫病理过程。②SARS-CoVS蛋白诱导IP-10在宿主细胞的生成不依赖IFN-γ。Objective ： To investigate the role of the recombinant S protein of SARS-CoV in the induction of chemokine IP-IO and other cytokines in airway epithelial ceils and immunocytes. Methods： Using insect-baculovirus expression system and Nickel affinity Magnet Beads, S protein of SARS-CoV was produced and then used to stimulate cultured human bronchial epithelial ceils （16HBE）, human peripheral blood mononuclear ceils （PBMC）, human peripheral blood monocytes and alveolar macrophages. The levels of IP-10 and the cytokines involved in immunoreaction in response to virus infection were detected in the supernatants of those cells cultured with the S protein by liquid Chip system. Results： Under normal condition, no detectable IP-10 was found in 16HBE. A high level of IP-10（79.97 ± 13.81 ） pg/ml was detected in the 16HBE 12 hrs after being treated with the S protein, and the induction of IP-10 by S protein displayed at a significant quantity-effect reaction, but not in PBMC, monocytes and alveolar macrophages. In contrast, IFN-γ was able to induce the production of IP-10 in either 16HBE or the immunocytes. Conclusion ： 1. S protein of SARS-CoV can induce a high level of IP-10 in lung epithelial cells at early stage after the virus infection, which may initiate the process of the immune damage in the lung. 2. S protein of SARS-CoV induces the production of IP-10 by a way of IFN-γ independent.

关 键 词：严重急性呼吸综合征 冠状病毒 S蛋白 支气管上皮细胞 

分 类 号：R563[医药卫生—呼吸系统]