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Bad Schmiedeberg, Germany

Lang K.,Witten/Herdecke University | Strell C.,Witten/Herdecke University | Niggemann B.,Witten/Herdecke University | Zanker K.S.,Witten/Herdecke University | And 4 more authors.
Microgravity Science and Technology | Year: 2010

In our project we developed a technical equipment which allows to visualize migration of cells in real-time video-microscopy during altered gravity conditions of NOVESPACE Airbus A300 ZERO-G parabolic flights. For validation of the experimental device we have used fast moving human neutrophils as example, because their migration is fundamental to keep the organism under immunological surveillance. Their migration is indispensable for immune effector function, where the cells leave the blood vessels and navigate to places of infection to fulfill their main task of phagocytosis. Thereby, we have analyzed if their migration is affected during altered gravity conditions and if pharmacological modification of cytoskeletal dynamics influences neutrophil migratory activity. Whereas we detected no change in neutrophil locomotory behaviour in microgravity, we found a significant inhibitory influence of hypergravity, irrespective of the chemical stimulus used. Our results suggest that hypergravity, following a microgravity environment, could represent a hazard to the human immune system function. Thus, our cell migration assay offers an optimum experimental device for studying the migratory activity and underlying signal transduction mechanisms of neutrophils to assess the immunological fitness of humans in space to fight infection, but also for investigating the locomotion of other cell types or unicellular organisms such as ciliates. © 2009 Springer Science+Business Media B.V. Source

Ullrich O.,University of Zurich | Ullrich O.,Otto Von Guericke University of Magdeburg | Studer M.,University of Zurich | Thiel C.,University of Zurich | And 10 more authors.
61st International Astronautical Congress 2010, IAC 2010 | Year: 2010

Long-term sensitivity of human cells to reduced gravity has been supposed since the first Apollo missions and was demonstrated during several space missions in the past. However, little information is available on primary and rapid gravi-responsive elements in mammalian cells. In search of rapid-responsive molecular alterations in mammalian cells, short-term microgravity provided by parabolic flight maneuvers is an ideal way to elucidate such initial and primary effects. Modern biomedical research at the cellular and molecular level requires frequent repetition of experiments which are usually performed in sequences of experiments and analyses. Therefore, a research platform on Earth providing frequent, easy and repeated access to real microgravity for cell culture experiments is strongly desired. For this reason, we developed a research platform onboard the military fighter jet aircraft Northrop F-5E "Tiger II". The experimental system consists of a programmable and automatically operated system composed of six individual experiment modules, placed in the front compartment which work completely independent of the aircraft systems. Signal transduction pathways in cultured human cells can be investigated after the addition of an activator solution at the onset of microgravity and a fixative or lysis buffer after termination of microgravity. Before the beginning of a regular military training flight, a parabolic maneuver was executed. After a 1g control phase, the parabolic maneuver starts at 13000ft and at Mach 0.99 airspeed, following a free-fall ballistic Keplerian trajectory lasting 45 seconds with an apogee of 27000ft at Mach 0.4 airspeed. Temperature, pressure and acceleration are monitored constantly during the entire flight. Cells and activator solutions are kept at 37°C during the entire experiment until the fixative has been added. The parabolic flight profile provides up to 45s of microgravity at a quality of 0.05g in all axes. Access time is 30min before take-off; retrieval time is 30min after landing. We conclude that using military fighter jets for microgravity research is a valuable tool for frequent and repeated cell culture experiments and therefore for state-of-the art method of biomedical research. Source

Paulsen K.,University of Zurich | Thiel C.,University of Munster | Timm J.,University of Zurich | Schmidt P.M.,CSIRO | And 15 more authors.
Acta Astronautica | Year: 2010

Since decades it is known that the activity of cells of the immune system is severely dysregulated in microgravity, however, the underlying molecular aspects have not been elucidated yet. The identification of gravity-sensitive molecular mechanisms in cells of the immune system is an important and indispensable prerequisite for the development of counteractive measures to prevent or treat disturbed immune cell function of astronauts during long-term space missions. Moreover, their sensitivity to altered gravity renders immune cells an ideal model system to understand if and how gravity on Earth is required for normal mammalian cell function and signal transduction. We investigated the effect of simulated weightlessness (2D clinostat) and of real microgravity (parabolic flights) on key signal pathways in a human monocytic and a T lymphocyte cell line. We found that cellular responses to microgravity strongly depend on the cell-type and the conditions in which the cells are subjected to microgravity. In Jurkat T cells, enhanced phosphorylation of the MAP kinases ERK-1/2, MEK and p38 and inhibition of nuclear translocation of NF-kB were the predominant responses to simulated weightlessness, in either stimulated or non-stimulated cells. In contrast, non-stimulated monocytic U937 cells responded to simulated weightlessness with enhanced overall tyrosine-phosphorylation and activation of c-jun, whereas PMA-stimulated U937 cells responded the opposite way with reduced tyrosine-phosphorylation and reduced activation of c-jun, compared with PMA-stimulated 1g controls. P53 protein was phosphorylated rapidly in microgravity. The identification of gravi-sensitive mechanisms in cells of the immune system will not only enable us to understand and prevent the negative effects of long time exposure to microgravity on Astronauts, but could also lead to novel therapeutic targets in general. © 2010 Elsevier Ltd. All rights reserved. Source

Paulsen K.,University of Zurich | Tauber S.,University of Zurich | Tauber S.,Universitatsplatz 2 | Dumrese C.,University of Zurich | And 30 more authors.
BioMed Research International | Year: 2015

Cells of the immune system are highly sensitive to altered gravity, and the monocyte as well as the macrophage function is proven to be impaired under microgravity conditions. In our study, we investigated the surface expression of ICAM-1 protein and expression of ICAM-1 mRNA in cells of the monocyte/macrophage system in microgravity during clinostat, parabolic flight, sounding rocket, and orbital experiments. In murine BV-2 microglial cells, we detected a downregulation of ICAM-1 expression in clinorotation experiments and a rapid and reversible downregulation in the microgravity phase of parabolic flight experiments. In contrast, ICAM-1 expression increased in macrophage-like differentiated human U937 cells during the microgravity phase of parabolic flights and in long-term microgravity provided by a 2D clinostat or during the orbital SIMBOX/Shenzhou-8 mission. In nondifferentiated U937 cells, no effect of microgravity on ICAM-1 expression could be observed during parabolic flight experiments. We conclude that disturbed immune function in microgravity could be a consequence of ICAM-1 modulation in the monocyte/macrophage system, which in turn could have a strong impact on the interaction with T lymphocytes and cell migration. Thus, ICAM-1 can be considered as a rapid-reacting and sustained gravity-regulated molecule in mammalian cells. © 2015 Katrin Paulsen et al. Source

Thiel C.S.,University of Zurich | Thiel C.S.,Universitatsplatz 2 | Thiel C.S.,Otto Von Guericke University of Magdeburg | Hauschild S.,University of Zurich | And 25 more authors.
BioMed Research International | Year: 2015

Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes (housekeeping genes) are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity. © 2015 Cora S. Thiel et al. Source

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