Data from: Cytoskeletal stability and metabolic alterations in primary human macrophages in long-term microgravity

The immune system is one of the most affected systems of the human body during space flight. The cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the functions of immune cells. The CELLBOX-PRIME (= CellBox-Primary Human Macrophages in Microgravity Environment) experiment investigated for the first time microgravity-associated long-term alterations in primary human macrophages, one of the most important effector cells of the immune system. The experiment was conducted in the U.S. National Laboratory on board of the International Space Station ISS using the NanoRacks laboratory and Biorack type I standard CELLBOX EUE type IV containers. Upload and download were performed with the SpaceX CRS-3 and the Dragon spaceship on April 18th, 2014 / May 18th, 2014. Surprisingly, primary human macrophages exhibited neither quantitative nor structural changes of the actin and vimentin cytoskeleton after 11 days in microgravity when compared to 1g controls. Neither CD18 or CD14 surface expression were altered in microgravity, however ICAM-1 expression was reduced. The analysis of 74 metabolites in the cell culture supernatant by GC-TOF-MS, revealed eight metabolites with significantly different quantities when compared to 1g controls. In particular, the significant increase of free fucose in the cell culture supernatant was associated with a significant decrease of cell surface-bound fucose. The reduced ICAM-1 expression and the loss of cell surface-bound fucose may contribute to functional impairments, e.g. the activation of T cells, migration and activation of the innate immune response. We assume that the surprisingly small and non-significant cytoskeletal alterations represent a stable "steady state" after adaptive processes are initiated in the new microgravity environment. Due to the utmost importance of the human macrophage system for the elimination of pathogens and the clearance of apoptotic cells, its apparent robustness to a low gravity environment is crucial for human health and performance during long-term space missions.

免疫系统是人体在航天飞行期间受影响最显著的系统之一。免疫细胞对微重力环境异常敏感。由此引发了严峻的担忧：航天飞行导致的免疫系统弱化是否会最终阻碍人类在地外轨道之外拓展生存空间。对于载人航天而言，阐明重力改变如何影响并改变免疫细胞功能的细胞与分子机制，是一项迫切需求。CELLBOX-PRIME（全称：微重力环境下人原代巨噬细胞CellBox-Primary Human Macrophages in Microgravity Environment）实验首次探究了微重力相关的人原代巨噬细胞（primary human macrophages）长期改变——巨噬细胞是免疫系统最重要的效应细胞之一。该实验于搭载于国际空间站（International Space Station, ISS）的美国国家实验舱内开展，使用了NanoRacks实验室设备以及Biorack I型标准CELLBOX EUE IV型容器。载荷的上行与下行分别于2014年4月18日与2014年5月18日通过SpaceX CRS-3任务及龙（Dragon）飞船完成。令人意外的是，与1g重力对照组相比，经11天微重力暴露的人原代巨噬细胞，其肌动蛋白（actin）与波形蛋白（vimentin）细胞骨架既未出现定量变化，也未发生结构改变。CD18与CD14的表面表达均未受微重力影响，但细胞间黏附分子1（ICAM-1）的表达水平有所下调。通过GC-TOF-MS（气相色谱-飞行时间质谱）对细胞培养上清液中的74种代谢物进行分析后发现，与1g对照组相比，有8种代谢物的含量存在显著差异。其中，细胞培养上清液中游离岩藻糖的显著升高，与细胞表面结合岩藻糖的显著降低存在关联。ICAM-1表达下调以及细胞表面结合岩藻糖的缺失，可能会导致多种功能损伤，例如T细胞活化、固有免疫应答的迁移与激活过程。我们认为，此次观测到的意外轻微且无统计学显著性的细胞骨架改变，代表了在新的微重力环境中启动适应过程后所达到的稳定“稳态”。鉴于人类巨噬细胞系统在清除病原体与凋亡细胞过程中至关重要，其对低重力环境表现出的表观稳定性，对于长期航天任务期间的人体健康与作业能力而言至关重要。