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Gravity Sensitivity of T-Cell Activation : The Actin Cyto-Skeleton.

B.B. Hashemi1,2, J.E. McClure1,2, and D.L. Pierson1. 1Life Science Research Laboratories, NASA - Johnson Space Center, Houston, TX 77058, and 2National Space Biomedical Research Institute, Baylor College of Medicine, Houston TX 77030.

Experiments performed during space flight indicate an inhibition of human peripheral T-cell activation in microgravity culture [Hashemi et. al. FASEB J. 1999 13, (4) 2071].  This inhibition correlates with a lack of activation-induced polarization of the Microtubule Organizing Center (MTOC) towards the activation site.  The results indicate that changes in the gravity environment of T-cells from 1g can have dramatic effects on their functional responses.

The actin cytoskeleton plays a crucial role in signal transduction and activation response of T-cells [Destin et. al. Nature Immunology 2000 1, (1) 23].  In the current study, we evaluate the polymerization state of actin in the Jurkat Leukemia T-cell line cultured under hypogravity and hypergravity conditions.  When Jurkat cells are exposed to hypogravity culture by clinorotation, they exhibit an impairment in the activation-induced polymerization of F-actin; a response that occurs readily in T-cells that are cultured in 1g.  Furthermore, exposure of T cells to hypergravity culture has a dramatic effect on the actin cytoskeleton.  A 30-minute exposure of Jurkat cells to as little as a 2g hypergravity culture results in a significant decrease in cellular F-actin.  Exposure to higher centrifugal forces in the range of 100-300g for as little as 10 minutes results in substantially lower levels of cellular F-actin.  These results are consistent with our earlier findings of inhibition of T-cell activation responses during space flight, and they have significant implications for gravitational biology as they suggest an important role for the actin cytoskeleton in gravity sensitivity of T-cell activation.


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