Signal transduction in primary XXXX T lymphocytes in altered gravity during parabolic flight and clinostat experiments.

@entity1 @entity6755 @entity2902
BACKGROUND/AIMS: Several limiting factors for @entity1 health and performance in microgravity have been clearly identified arising from the immune system, and substantial research activities are required in order to provide the basic information for appropriate integrated risk management. The gravity-sensitive nature of cells of the immune system renders them an ideal biological model in search for general gravity-sensitive mechanisms and to understand how the architecture and function of @entity1 cells is related to the gravitational force and therefore adapted to life on Earth. METHODS: We investigated the influence of altered gravity in parabolic flight and 2D clinostat experiments on key proteins of activation and signaling in primary T lymphocytes. We quantified components of the signaling cascade 1.) in non-activated T lymphocytes to assess the "basal status" of the cascade and 2.) in the process of activation to assess the signal transduction. RESULTS: We found a rapid decrease of CD3 and @entity2902 surface expression and reduced p-LAT after 20 seconds of altered gravity in non-activated primary T lymphocytes during parabolic flight. Furthermore, we observed decreased CD3 surface expression, reduced @entity6755 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of @entity2902 during 60 minutes of clinorotation. CONCLUSION: CD3 and @entity2902 are downregulated in primary T lymphocytes in altered gravity. We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes.    2015 S. Karger AG, Basel.
