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 |
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Authors: | Katrin Paulsen,Svantje Tauber,Nadine Goelz,Dana Michaela Simmet,Stephanie Engeli,Maria Birlem,Claudia Dumrese,Anissja Karer,Sandra Hunziker,Josefine Biskup,Shalimar Konopasek,Durie Suh,Eva Hü rlimann,Christoph Signer,Anna Wang,Chen Sang,Karl-Heinrich Grote,Fengyuan Zhuang,Oliver Ullrich |
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Affiliation: | 1. Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland;2. Department of Machine Design (IMK), Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, D-39106 Magdeburg, Germany;3. EADS Astrium Space Transportation, Claude-Dornier-Strasse 1, D-88090 Immenstaad, Germany;4. Center for Microscopy and Image Analysis, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland;5. School of Biological Science and Medical Engineering, Beihang University, 37 Xueyuan Road, Beijing 100191, China;6. School of Life Sciences, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China;g Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland |
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Abstract: | 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. |
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Keywords: | CC, cell culture chamber CMSEO, China manned space engineering office DLR, German Aerospace Center GESSA, General Establishment of Space Science Application ESA, European Space Agency EUE, experiment unique equipments HEPES, N-2-hydroxyethylpiperazine-N&prime -2-ethanesulfonic acid H/W, Hardware ISS, International Space Station JSLC, Jiuquan Satellite Launch Center LFA-1, leukocyte function-associated antigen-1 LT, local time MAC-1/CR3, macrophage antigen-1/complement receptor 3 μg, microgravity PEEK, polyether ether ketone PFA, paraformaldehyde PMA, 12-O-tetradecanoylphorbol-13-acetate PITC, payload integration and test center TCC, test culture chambers TUNEL, TdT-mediated dUTP- biotin nick end labeling SIMBOX, Science in Microgravity Box UTC, Coordinated Universal Time |
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