FPR2在PM2.5污染物诱导的慢性阻塞性肺部(COPD)模型中的免疫调节作用研究

项目名称： FPR2在PM2.5污染物诱导的慢性阻塞性肺部(COPD)模型中的免疫调节作用研究

项目编号： No.31470844

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 陈克强

作者单位： 同济大学

项目金额： 80万元

中文摘要： 慢性阻塞性肺病(COPD)是呼吸系统常见病，其发病与大气污染密切相关。污染物PM2.5可激活肺部巨噬细胞产生炎症因子和趋化因子，激活和募集树突细胞，导致COPD发病及恶化。研究表明巨噬细胞表达的血清淀粉蛋白A(SAA)与COPD密切相关。FPR2是SAA等趋化因子的受体，调控免疫细胞的活化及募集。我们的前期研究发现，FPR2对树突细胞在肺部炎症反应中的募集起关键调控作用。然而，在COPD发病中，巨噬细胞在PM2.5刺激下所分泌的SAA是否通过FPR2调控树突细胞激活和募集仍不明确。我们拟利用PM2.5诱导小鼠COPD发病的模型，结合树突细胞特异性敲除小鼠、骨髓移植等手段，从分子、细胞和整体水平上深入研究污染物所致COPD发病中SAA通过FPR2调控树突细胞激活和募集的分子机制。本项目的完成将为阐明空气污染物所致的COPD发病机理提供理论依据，为COPD防治提供新靶点。

中文关键词： 甲酰肽受体2；PM2.5；COPD；免疫调节

英文摘要： Chronic obstructive pulmonary disease (COPD), one of the most common lung diseases, has been associated with exposure to air pollution. The particular matter (PM2.5) in the air pollution can activate alveolar macrophages to produce cytokines and chemokines, which subsequently activate and recruit dendritic cells (DCs) to the lung and result COPD exacerbation. Serum amyloid protein A (SAA) has been shown to be a candidate mediator of COPD inflammation. SAA can be recognized by FPR2, which is known to be important in leukocyte chemotaxis and recruitment. Previous work of the applicant has revealed that FPR2 plays an important role in DCs recruitment in inflammatory lung disease. However, in PM2.5 induced COPD, whether SAA secreted by macrophages regulates DCs activation through FPR2 still remains unclear. On the basis of previous work, our project will investigate the molecular mechanisms by which SAA regulates FPR2-mediated DCs activation and recruitment in the model of PM2.5 induced COPD. The models of tissue-specific knockout mice and bone marrow transfer will allow us to understand the mechanism at levels of the molecular, cellular and whole organism. The result will provide important theoretical basis for prevention and therapeutics of COPD.

英文关键词： FPR2;PM2.5;COPD;immune regulation