摘要
本研究旨在明确一氧化氮(NO)在恶性胸腔积液(MPE)形成中的作用,探究NO是否调控MPE中Th1/Th17免疫反应.利用在野生型(WT)小鼠(Mus musculus)及诱导型一氧化氮合酶敲除(NOS2-/-)小鼠的胸膜腔内注射肺腺癌细胞或肠腺癌细胞,建立MPE模型.明确小鼠MPE中NO的含量;分析并比较WT及NOS2^(-/-)小鼠的胸水量及生存期的差异;检测NO对胸膜血管通透性的影响;以及NO对MPE中Th1及Th17细胞的影响.研究结果显示,NO在WT小鼠恶性胸腔积液中的含量显著高于外周血.与WT小鼠相比,NOS2-/-小鼠的胸膜血管通透性增强,胸水量增加,生存期缩短,其MPE中Th1细胞比例降低,而Th17细胞比例升高.NO可促进Th1细胞的分化,抑制Th17细胞的分化.本研究证实了NO通过影响MPE小鼠胸膜血管通透性而抑制MPE的形成,NO可促进Th1细胞的分化并抑制Th17细胞的分化,从而调节MPE中Th1/Th17细胞免疫反应.
In the present study, we were prompted to investigate the effect of NO signaling on the formation of malignant pleural effusion（MPE）and determined whether NO affects Th1/Th17 response in MPE. The development of MPE and survival of MPE mice were compared between wild-type and NOS2^-/-mice. The effect of NOS2 on vascular permeability of pleura and differentiation of Th1 and Th17 in MPE was also explored. Our current data show that production of NO is significantly enhanced in MPE as compared with peripheral circulation, and that nitric oxide synthase-2（NOS2） deficiency increases pleural vascular permeability and thus promotes the development of MPE, and reduces the survival of mice bearing MPE. NOS2 deficiency inhibits Th1 cell differentiation and promotes Th17 cell differentiation. Our data provide the first evidence that NO inhibits MPE formation by inhibiting fluid extravasation into the pleural space and by promoting Th1 cell differentiation and suppressing Th17 cell differentiation. Overall, our results shed light on the mechanisms by which NO suppresses MPE formation, providing a promising therapeutic strategy in the management of MPE.
作者
姜帅
吴秀芝
翟侃
伊凤双
王臻
王政
叶志坚
杨卫兵
施焕中
JIANG Shuai;WU Xiu Zhi;ZHAI Kan;YI Feng Shuang;WANG Zhen;WANG Zheng;YE Zhi Jian;YANG Wei Bing;SHI Huan Zhong(Department of Respiratory and Critical Care Medicine,Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Department of Respiratory Medicine,First People＇s Hospital of Foshan,Sun Yat-sen University,Foshan 528000,China;Department of Respiratory and Critical Care Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)
出处
《中国科学：生命科学》
CSCD
北大核心
2018年第7期795-801,共7页
Scientia Sinica(Vitae)
基金
国家自然科学基金(批准号:31470883
81600070
81400069和31670920)资助
