失重条件下Arp2/3调控细胞骨架重排对巨噬细胞重力响应的影响机理研究

Space microgravity environment（weightlessness） is associated with immunological alterations, while the decreased phagocytosis activity of macrophages has been specially noticed. The cytoskeleton plays a significant role in phagocytosis of macrophages and it is directly regulated by Arp2/3 (actin-related protein 2/3 complex). Our previous study has confirmed that simulated weightlessness can decrease the phagocytosis activity of human macrophages. Furthermore, we found this modulation resulting from the down-regulation of Arp2/3.Thus, we present a hypothesis that as the key molecular regulating the cytoskeleton of macrophages, Arp2/3 may play an important role in responding to different gravity and immunity decreasing of macrophages. Therefore, we plan to simulate weightlessness by superconducting magnet and stochastic gyroscope, (1) study the effects of simulated weightlessness on mechanical and biological characteristics of macrophages under the molecular-cell level,(2) establish the finite element model of macrophages and analyze the mechanical features of macrophages under simulated weightlessness, (3) study the relationship between the alteration of the expression, distribution of Arp2/3 in macrophages and the alteration of the mechanical and biological characteristics of macrophages. To compare the differences of features between macrophages under normal gravity and simulated weightlessness, our results will provide experimental data for finely revealing the mechanisms of Arp2/3 in the process of responding to different gravity of macrophages, and provide a theoretical basis for the study of immune protection measures of astronauts and people in some special environments on the ground.

空间失重环境可导致人体免疫力下降，其中巨噬细胞活性下降尤为突出。巨噬细胞骨架结构在维持其吞噬功能中发挥重要作用，而它受到Arp2/3(肌动蛋白相关蛋白2/3复合物)的直接调控。申请者前期实验证实模拟失重下巨噬细胞吞噬活性下降，且发现与Arp2/3表达下调有关，因此提出：Arp2/3作为调控细胞骨架结构的关键分子，可能在失重环境下巨噬细胞对重力的响应及免疫功能抑制中发挥重要作用。 本项目拟利用超导磁体和随机回转仪模拟失重环境，（1）从分子-细胞水平研究模拟失重环境对巨噬细胞力学、生物学特性的影响规律；（2）建立巨噬细胞有限元模型并对模拟失重环境下力学特性进行分析；（3）Arp2/3表达分布改变与巨噬细胞力学、生物学特性变化的相关性。比较分析正常重力和模拟失重环境细胞特性的差异，为阐明Arp2/3在巨噬细胞重力响应中的作用机理提供实验数据，为航天员和地面处于特殊环境人群的免疫防护提供理论依据。

空间失重环境可导致人体免疫力下降，其中巨噬细胞活性下降尤为突出。巨噬细胞骨架结构在维持其吞噬功能中发挥重要作用，而它受到Arp2/3(肌动蛋白相关蛋白2/3复合物)的直接调控。申请者通过实验证实模拟失重下巨噬细胞吞噬活性下降，且发现与Arp2/3表达下调有关，并且确证了：Arp2/3作为调控细胞骨架结构的关键分子，在失重环境下巨噬细胞对重力的响应及免疫功能抑制中发挥重要作用。.本项目拟利用超导磁体和随机回转仪模拟失重环境，（1）从分子-细胞水平研究模拟失重环境对巨噬细胞力学、生物学特性的影响规律；（2）建立了巨噬细胞有限元模型并对模拟失重环境下力学特性进行分析；（3）Arp2/3表达分布改变与巨噬细胞力学、生物学特性变化的相关性。比较分析了正常重力和模拟失重环境细胞特性的差异，为阐明Arp2/3在巨噬细胞重力响应中的作用机理提供实验数据，为航天员和地面处于特殊环境人群的免疫防护提供理论依据。