Tauber Svantje, Lauber Beatrice A, Paulsen Katrin, Layer Liliana E, Lehmann Martin, Hauschild Swantje, Shepherd Naomi R, Polzer Jennifer, Segerer Jürgen, Thiel Cora S, Ullrich Oliver
Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
Department of Machine Design, Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, Magdeburg, Germany.
PLoS One. 2017 Apr 18;12(4):e0175599. doi: 10.1371/journal.pone.0175599. eCollection 2017.
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.
免疫系统是人体在太空飞行期间受影响最严重的系统之一。免疫系统的细胞对微重力异常敏感。因此，人们严重担忧与太空飞行相关的免疫系统减弱是否最终会阻碍人类在地球轨道之外的活动扩展。对于载人航天飞行而言，迫切需要了解重力改变影响和改变免疫细胞功能的细胞和分子机制。CELLBOX-PRIME（=微重力环境下的原代人巨噬细胞细胞盒）实验首次研究了原代人巨噬细胞中与微重力相关的长期变化，原代人巨噬细胞是免疫系统最重要的效应细胞之一。该实验在美国国家实验室的国际空间站（ISS）上进行，使用了NanoRacks实验室和Biorack I型标准CELLBOX EUE IV型容器。于2014年4月18日/2014年5月18日通过SpaceX CRS-3和龙飞船进行了装卸。令人惊讶的是，与1g重力对照组相比，原代人巨噬细胞在微重力环境中11天后，肌动蛋白和波形蛋白细胞骨架既没有发生数量上的变化，也没有结构上的改变。在微重力环境下，CD18或CD14的表面表达均未改变，但细胞间黏附分子-1（ICAM-1）的表达减少。通过气相色谱-飞行时间质谱（GC-TOF-MS）对细胞培养上清液中的74种代谢物进行分析，结果显示与1g重力对照组相比，有8种代谢物的含量存在显著差异。特别是，细胞培养上清液中游离岩藻糖的显著增加与细胞表面结合岩藻糖的显著减少有关。ICAM-1表达的降低和细胞表面结合岩藻糖的丧失可能导致功能受损，例如T细胞的激活、先天性免疫反应的迁移和激活。我们认为，令人惊讶的是，微小且不显著的细胞骨架改变代表了在新的微重力环境中启动适应性过程后的一种稳定“稳态”。由于人类巨噬细胞系统对于消除病原体和清除凋亡细胞至关重要，其对低重力环境的明显耐受性对于长期太空任务期间的人类健康和表现至关重要。
