肺泡巨噬细胞对烟雾暴露的差异性极化调节吸烟相关肺疾病的表型

项目名称： 肺泡巨噬细胞对烟雾暴露的差异性极化调节吸烟相关肺疾病的表型

项目编号： No.81470238

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 黄克武

作者单位： 首都医科大学

项目金额： 75万元

中文摘要： 肺气肿与肺纤维化均是异常的肺老化疾病，多与慢性香烟烟雾暴露有关。我们前期的实验研究发现，不同免疫背景的小鼠衰老时，可出现肺结构和功能的特异性改变。巨噬细胞处于衔接固有免疫与适应性免疫的关键环节，在体内外不同微环境的影响下，可分化出不同表型并表现出功能上的差异。在此，我们假设：肺泡巨噬细胞对烟雾暴露的差异性极化调节吸烟相关肺疾病的表型。为了验证上述假说，首先取肺气肿、IPF患者的BALF，利用体外分离、培养肺泡巨噬细胞，借助Real-Time PCR和ELISA等技术，确定不同患者间存在肺泡巨噬细胞极化的差异；然后，利用不用免疫背景的小鼠，动态观察在慢性香烟烟雾暴露的不同时期肺泡巨噬细胞的极化以及同期肺结构与功能的变化，并研究肺泡极化巨噬细胞的来源及可能的分子信号通路。该项目的实施将有助于丰富对肺气肿和IPF发展机制的认识，并为治疗相关肺疾病提供新途径。

中文关键词： 肺泡巨噬细胞；极化；肺气肿；肺纤维化

英文摘要： Emphysema and pulmonary fibrosis are diseases related to abnormal lung aging, mostly caused by chronic exposure to cigarette smoke. Our previous studies showed that mice with different immune background had specific changes of lung structure and function with senescence. Macrophages play an important role in innate and adaptive immunity. Macrophages can adopt a myriad of phenotypes and fulfill different function in tissues based on signals they receive from their environment. Herein, we hypothesize that diverse polarization of alveolar macrophages to smoke exposure mediate the phenotypes of cigarette smoke-induced lung diseases. To test this hypothesis, BALF will be collected from patients of emphysema and IPF, and the different polarization of alveolar macrophages between the two groups are identified by real-time PCR and ELISA in vitro. Then, the mice with different immune backgrounds are chronically exposed to cigarette-smoke, and the polarization of alveolar macrophages and changes of lung structure and function are observed dynamically at different exposure periods. Meanwhile,the resource of activated alveolar macrophage will be identified and the possible molecular signaling pathways be explored. The implementation of the project will help to enrich the mechanism for the development of emphysema and IPF, and benefit to open a new therapeutic approach in future.

英文关键词： alveolar macrophage;polarization;emphysema;pulmonary fibrosis