Space flight affects motility and cytoskeletal structures in human monocyte cell line J-111.

Certain functions of immune cells in returning astronauts are known to be altered. A dramatic depression of the mitogenic in vitro activation of human lymphocytes was observed in low gravity. T-cell activation requires the interaction of different type of immune cells as T-lymphocytes and monocytes. Cell motility based on a continuous rearrangement of the cytoskeletal network within the cell is essential for cell-cell contacts. In this investigation on the International Space Station we studied the influence of low gravity on different cytoskeletal structures in adherent monocytes and their ability to migrate. J-111 monocytes were incubated on a colloid gold substrate attached to a cover slide. Migrating cells removed the colloid gold, leaving a track recording cell motility. A severe reduction of the motility of J-111 cells was found in low gravity compared to 1g in-flight and ground controls. Cell shape appeared more contracted, whereas the control cells showed the typical morphology of migrating monocytes, i.e., elongated and with pseudopodia. A qualitative and quantitative analysis of the structures of F-actin, ß-tubulin and vinculin revealed that exposure of J-111 cells to low gravity affected the distribution of the different filaments and significantly reduced the fluorescence intensity of F-actin fibers. Cell motility relies on an intact structure of different cytoskeletal elements. The highly reduced motility of monocytes in low gravity must be attributed to the observed severe disruption of the cytoskeletal structures and may be one of the reasons for the dramatic depression of the in vitro activation of human lymphocytes.

Signal transduction in T cells: an overview.

The mitogenic in vitro activation of human peripheral blood lymphocytes is severely depressed in space as well as in models of low gravity conditions on ground. The mechanism of T-cell activation is very complex; 3 signals are required for full activation. A series of experiments performed in space and in modeled low gravity on ground have shown that a failure in the delivery of the second signal--interleukin-2--is one of the reasons for the impaired activation. The cytoskeleton plays a key role in several steps of the mitogenic activation; (1) in the binding of the mitogen to the cell membrane and the subsequent patching and capping of the receptors, and (2) in the transduction of the signals from the membrane to the nucleus. Changes in the cytoskeletal structures of vimentin and tubulin observed in cells exposed to low gravity conditions may have influenced the correct signal transduction.