Basic fibroblast growth factor protects against influenza A virus-induced acute lung injury by recruiting neutrophils  

作　　者：Keyu Wang Chengcai Lai Tieling Li Cheng Wang Wei Wang Bing Ni Changqing Bai Shaogeng Zhang Lina Han Hongjing Gu Zhongpeng Zhao Yueqiang Duan Xiaolan Yang Li Xing Lingna Zhao Shanshan Zhou Min Xia Chengyu Jiang Xiliang Wang Penghui Yang 

机构地区：[1]State Key Laboratory of Pathogens and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China [2]Chinese PLA General Hospital,Beijing 100853,China [3]State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Beijing 100005,China [4]Institute of Immunology,Third Military Medical University,Chongqing 400038,China [5]Beijing 307 Hospital of PLA Affiliated with the Chinese Academy of Medical Sciences,Beijing 100070,China [6]Beijing 302 Hospital of PLA,Beijing 100039,China

出　　处：《Journal of Molecular Cell Biology》2018年第6期573-585,共13页分子细胞生物学报（英文版）

基　　金：funding from the National High Technology Research and Development Program of China (SS2015AA020924);the National Natural Science Foundation of China (81771700);the Ministry of Science and Technology of China (2013ZXI0004003 and SS2012AA020905);the National Major Research and Development Program (2016YFA0502203 and 2017YFC1200800);P.Y.was supported by the Beijing Nova Program (Z141107001814054).

摘　　要：Influenza virus (IAV)infection is a major cause of severe respiratory illness that affects almost every country in the world.IAV infections result in respiratory illness and even acute lung injury and death,but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated.In this study,the basic fibroblast growth factor 2 (FGF2)level was markedly increased in H1N1 virus-infected humans and mice.FGF2,which is predominately derived from epithelial cells,recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFKB signaling pathway.FGF2 depletion or knockout exacerbated influenzaassociated disease by impairing neutrophil recruitment and activation.More importantly,administration of the recombinant FGF2 protein significantly aUeviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice.Based on the results from experiments in which neutrophils were depleted and adoptively transferred,FGF2 protected mice against IAV , infection by recruiting neutrophils.Thus,FGF2 plays a critical role in preventing IAV-induced lung injury,and FGF2 is a promising potential therapeutic target during IAV infection.

关 键 词：influenza H1N1 virus recombinant FGF2 protein neutrophil recruitment FGFR2-PI3K-AKT-NFκB signaling therapeutic target 

分 类 号：Q[生物学]