Abstract
We investigated the influence of altered gravity on key proteins of T cell activation during the MASER-12 ballistic suborbital rocket mission of the European Space Agency (ESA) and the Swedish Space Cooperation (SSC) at ESRANGE Space Center (Kiruna, Sweden). We quantified components of the T cell receptor, the membrane proximal signaling, MAPK-signaling, IL-2R, histone modifications and the cytoskeleton in non-activated and in ConA/CD28-activated primary human T lymphocytes. The hypergravity phase during the launch resulted in a downregulation of the IL-2 and CD3 receptor and reduction of tyrosine phosphorylation, p44/42-MAPK phosphorylation and histone H3 acetylation, whereas LAT phosphorylation was increased. Compared to the baseline situation at the point of entry into the microgravity phase, CD3 and IL-2 receptor expression at the surface of non-activated T cells were reduced after 6 min microgravity. Importantly, p44/42-MAPK-phosphorylation was also reduced after 6 min microgravity compared to the 1g ground controls, but also in direct comparison between the in-flight μg and the 1g group. In activated T cells, the reduced CD3 and IL-2 receptor expression at the baseline situation recovered significantly during in-flight 1g conditions, but not during microgravity conditions. Beta-tubulin increased significantly after onset of microgravity until the end of the microgravity phase, but not in the in-flight 1g condition. This study suggests that key proteins of T cell signal modules are not severely disturbed in microgravity. Instead, it can be supposed that the strong T cell inhibiting signal occurs downstream from membrane proximal signaling, such as at the transcriptional level as described recently. However, the MASER-12 experiment could identify signal molecules, which are sensitive to altered gravity, and indicates that gravity is obviously not only a requirement for transcriptional processes as described before, but also for specific phosphorylation / dephosphorylation of signal molecules and surface receptor dynamics.
Highlights
Gravity has been a constant force throughout evolutionary history on Earth
In this study we investigated the influence of altered gravity on key proteins and early signal transduction events of T cell activation
Samples were integrated in a late access unit (LAU) that was integrated into the rocket payload only 4 hours before launch and retrieved within 2 hours after landing
Summary
Gravity has been a constant force throughout evolutionary history on Earth. one of the fundamental biological questions is how the architecture and function of human cells are related to the gravitational force and Beginning already in the early days of human spaceflight, an enhanced susceptibility to infections has been observed among astronauts and frequently reported on: During space flights or very soon after returning to the earth astronauts of the Apollo missions suffered from bacterial and viral infections [1,2], while latent viruses such as varicella zoster were reactivated [3,4]. Subsequent in vitro experiments during the first Spacelab-Mission could demonstrate that the proliferative response of lymphocytes to mitogenic stimulation was strongly impaired under space conditions [7] This impairment of lymphocyte activation and the resulting immune deficiency is discussed as a serious limitation for manned long-term space flights [8], where the extraordinary psychological stress in a confined environment and the enhanced radiation, and the reduced gravity represent a major and direct “stress factor” at the cellular level. Because the IL-2 receptor transduces major proliferative signals in activated T cells, the diminished proliferative response of T cells upon stimulation during microgravity [7,9] could be caused by a reduced expression of IL-2, resulting in an impairment of positive regulatory feedback loops. Whereas the phenomenon of reduced activation of T cells during microgravity is well described and verified [5,7,9,12,13,14,15,16,17,18,19,20,21,22], the exact molecular mechanisms are not elucidated
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