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Severe disruption of the cytoskeleton and immunologically relevant surface molecules in a human macrophageal cell line in microgravity — Results of an in vitro experiment on board of the Shenzhou-8 space mission

机译:微重力严重破坏人类巨噬细胞细胞系中的细胞骨架和免疫相关表面分子—神舟八号太空飞行任务的体外实验结果

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摘要

During spaceflight the immune system is one of the most affected systems of the human body. During the SIMBOX (Science in Microgravity Box) mission on Shenzhou-8, we investigated microgravity-associated long-term alterations in macrophageal cells, the most important effector cells of the immune system. We analyzed the effect of long-term microgravity on the cytoskeleton and immunologically relevant surface molecules. Human U937 cells were differentiated into a macrophageal phenotype and exposed to microgravity or 1g on a reference centrifuge on-orbit for 5 days. After on-orbit fixation, the samples were analyzed with immunocytochemical staining and confocal microscopy after landing. The unmanned Shenzhou-8 spacecraft was launched on board a Long March 2F (CZ-2F) rocket from the Jiuquan Satellite Launch Center (JSLC) and landed after a 17-day-mission. We found a severely disturbed actin cytoskeleton, disorganized tubulin and distinctly reduced expression of CD18, CD36 and MHC-II after the 5 days in microgravity. The disturbed cytoskeleton, the loss of surface receptors for bacteria recognition, the activation of T lymphocytes, the loss of an important scavenger receptor and of antigen-presenting molecules could represent a dysfunctional macrophage phenotype. This phenotype in microgravity would be not capable of migrating or recognizing and attacking pathogens, and it would no longer activate the specific immune system, which could be investigated in functional assays. Obviously, the results have to be interpreted with caution as the model system has some limitations and due to numerous technical and biological restrictions (e.g. 23 °C and no CO2 supply during in-flight incubation). All parameter were carefully pre-tested on ground. Therefore, the experiment could be adapted to the experimental conditions available on Shenzhou-8.
机译:在太空飞行期间,免疫系统是人体受影响最严重的系统之一。在神舟八号的SIMBOX(微重力箱中的科学)任务中,我们研究了巨噬细胞中微重力相关的长期变化,巨噬细胞是免疫系统最重要的效应细胞。我们分析了长期微重力对细胞骨架和免疫相关表面分子的影响。将人U937细胞分化为巨噬细胞表型,并在参考重力离心机在轨暴露于微重力或1g的情况下5天。在轨固定后,在着陆后用免疫细胞化学染色和共聚焦显微镜分析样品。无人驾驶的神舟八号飞船是从酒泉卫星发射中心(JSLC)上搭载的长征2F(CZ-2F)火箭发射的,经过17天的任务后降落。我们发现微重力作用5天后,肌动蛋白的细胞骨架受到严重干扰,微管蛋白紊乱,CD18,CD36和MHC-II的表达明显降低。紊乱的细胞骨架,用于细菌识别的表面受体的丧失,T淋巴细胞的活化,重要的清除剂受体和抗原呈递分子的丧失可能代表功能异常的巨噬细胞表型。微重力中的这种表型将不能迁移或识别和攻击病原体,并且将不再激活特异性免疫系统,可以在功能测定中进行研究。显然,由于模型系统存在一定局限性,并且由于众多技术和生物学限制(例如23°C且在飞行中没有二氧化碳供应),因此必须谨慎解释结果。所有参数都在地面上经过了仔细的预测试。因此,该实验可以适应神舟八号上可用的实验条件。

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