Brungs Sonja, Kolanus Waldemar, Hemmersbach Ruth
Biomedical Research Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Koeln, Germany.
Molecular Immunology, LIMES Institute, University of Bonn, Carl-Troll Str. 31, 53115, Bonn, Germany.
Cell Commun Signal. 2015 Feb 3;13:9. doi: 10.1186/s12964-015-0088-8.
The recognition of pathogen patterns followed by the production of reactive oxygen species (ROS) during the oxidative burst is one of the major functions of macrophages. This process is the first line of defence and is crucial for the prevention of pathogen-associated diseases. There are indications that the immune system of astronauts is impaired during spaceflight, which could result in an increased susceptibility to infections. Several studies have indicated that the oxidative burst of macrophages is highly impaired after spaceflight, but the underlying mechanism remained to be elucidated. Here, we investigated the characteristics of reactive oxygen species production during the oxidative burst after pathogen pattern recognition in simulated microgravity by using a fast-rotating Clinostat to mimic the condition of microgravity. Furthermore, spleen tyrosine kinase (Syk) phosphorylation, which is required for ROS production, and the translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) to the nucleus were monitored to elucidate the influence of altered gravity on macrophage signalling.
Simulated microgravity leads to significantly diminished ROS production in macrophages upon zymosan, curdlan and lipopolysaccharide stimulation. To address the signalling mechanisms involved, Syk phosphorylation was examined, revealing significantly reduced phosphorylation in simulated microgravity compared to normal gravity (1 g) conditions. In contrast, a later signalling step, the translocation of NF-κB to the nucleus, demonstrated no gravity-dependent alterations.
The results obtained in simulated microgravity show that ROS production in macrophages is a highly gravisensitive process, caused by a diminished Syk phosphorylation. In contrast, NF-κB signalling remains consistent in simulated microgravity. This difference reveals that early signalling steps, such as Syk phosphorylation, are affected by microgravity, whereas the lack of effects in later steps might indicate adaptation processes. Taken together, this study clearly demonstrates that macrophages display impaired signalling upon pattern recognition when exposed to simulated microgravity conditions, which if verified in real microgravity this may be one reason why astronauts display higher susceptibility to infections.
巨噬细胞的主要功能之一是在氧化爆发过程中识别病原体模式并随后产生活性氧（ROS）。这一过程是第一道防线，对于预防病原体相关疾病至关重要。有迹象表明，宇航员的免疫系统在太空飞行期间会受到损害，这可能导致感染易感性增加。多项研究表明，太空飞行后巨噬细胞的氧化爆发受到严重损害，但其潜在机制仍有待阐明。在此，我们使用快速旋转的回转器模拟微重力条件，研究了病原体模式识别后模拟微重力下氧化爆发过程中产生活性氧的特征。此外，监测了ROS产生所需的脾酪氨酸激酶（Syk）磷酸化以及活化B细胞核因子κB（NF-κB）向细胞核的转位，以阐明重力改变对巨噬细胞信号传导的影响。
模拟微重力导致酵母聚糖、可德胶和脂多糖刺激后巨噬细胞中ROS产生显著减少。为了研究其中涉及的信号传导机制，检测了Syk磷酸化，结果显示与正常重力（1g）条件相比，模拟微重力下磷酸化显著降低。相比之下，后期的信号传导步骤，即NF-κB向细胞核的转位，未显示出重力依赖性改变。
在模拟微重力下获得的结果表明，巨噬细胞中ROS的产生是一个高度重力敏感的过程，是由Syk磷酸化减少引起的。相比之下，NF-κB信号传导在模拟微重力下保持一致。这种差异表明，早期信号传导步骤，如Syk磷酸化，受到微重力的影响，而后期步骤缺乏影响可能表明存在适应过程。综上所述，本研究清楚地表明，巨噬细胞在暴露于模拟微重力条件下进行模式识别时信号传导受损，如果在实际微重力中得到验证，这可能是宇航员感染易感性较高的一个原因。
