应用质谱成像技术原位表征肺癌组织区域的巨噬细胞免疫特性

项目名称： 应用质谱成像技术原位表征肺癌组织区域的巨噬细胞免疫特性

项目编号： No.91542101

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 李智立

作者单位： 中国医学科学院基础医学研究所

项目金额： 70万元

中文摘要： 病理微环境中巨噬细胞的抗炎与促炎相互转化，预示其与周围介质分子的相互作用密切相关。本研究将利用质谱成像技术，建立表征组织器官区域巨噬细胞免疫特性的新技术;原位检测肺癌组织区域巨噬细胞代谢物及其周围介质分子,从代谢组角度探究不同病理微环境区域巨噬细胞代谢组与其周围介质分子的分子调控网络,研究巨噬细胞代谢物及其周围介质分子与病理微环境特性之间的关系；利用免疫组化方法检测微环境中代谢合成酶和巨噬细胞表型、分布和免疫功能；利用流式细胞仪检测体外诱导巨噬细胞和来自病理微环境的巨噬细胞表型和免疫功能，获得不同环境下巨噬细胞代谢关键分子与其免疫特性的关系，从巨噬细胞代谢组的角度认识病理微环境中巨噬细胞的多可塑性和极化性，获得巨噬细胞在促炎和抗炎转化过程中的关键分子或分子谱，为深入解析巨噬细胞异质性与肺癌发生之间关系提供直接证据，为认识巨噬细胞促瘤机制提供新的理论依据。

中文关键词： 质谱成像；肺癌；代谢组；巨噬细胞；组织微环境

英文摘要： The mutual transformation between anti- and pro-inflammation of macrophages in different pathological environments implies that the interactions between macrophages and their surrounding medium molecules may play important roles. This study plans to establish an novel technological platform to characterize immunological characteristics of macrophages in lung cancerous tissues based on our own established mass spectrometry imaging. To in-situ investigate metabolites of macrophages and their surrounding medium molecules in lung cancerous tissues; To establish the metabolic regulation networks between metabolome of macrophages and their surrounding medium molecules; To probe the relationships between metabolites of macrophages, their surrounding medium molecules, and pathological environments. Measuring the metabolome-related enzymes and phenotypes, distribution and immunological functions of macrophages in different environments using immunohistochemical assays and phenotypes and immunological functions of induced in vitro macrophages and macrophages from tissues using flow cytometry and ELISA assays is to obtain the relationships between important metabolic molecules of macrophages and immunological functions under different environmental conditions and to recognize the plasticity and polarizability of macrophages in different pathological environments in macrophage metabolome point of view. Obtaining the important molecules and molecular profiling which involve in the anti-and pro-inflammatory processes of macrophages would allow us to deeply understand the link between macrophage heterogeneity and occurrence of cancers and to deeply understand pro-tumor mechanisms of macrophages.

英文关键词： Mass spectrmetry imaging;Lung Cancer;Metabolome;Macrophage;Tissue microenviroment