Structural and functional changes in lymphocytes in microgravity

Impairment of the immunity in astronauts and cosmonauts even in short-term flights is a recognized risk. Long-term orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Since 1992 we are investigating the effect of modeled (MMG) and true microgravity on isolated lymphocytes in vitro. We had shown that modeled and true microgravity inhibit lymphocyte locomotion. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. At the same time polyclonal lymphocyte activation prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. Analysis of the relationship between activation deficits and the loss of locomotion in MG suggested a fundamental defect in signal transduction mechanism that was confirmed in further studies. FACS analysis showed that MMG selectively inhibits the expression of PKC isoforms. The decrease was most prominent and substantial in PKC ɛ, less obvious in PKC δ and almost marginal and insignificant in PKC α . Downregulation of PKC isoforms δ and ɛ was proven at the mRNA level by RT-PCR and at protein level by Western blot. We had also demonstrated that MMG selectively affects not only the expression but also the cell distribution of different PKC isoforms that may contribute to the impairment of signal transduction in MG. MMG inhibits programmed cell death (PCD) in lymphocytes. Inhibition was observed in two experimental models (PCD induced by gamma-radiation in PBMC and activation-induced PCD in activated T cells after restimulation with PHA-M or PMA+ionomycin.). Comparative DNA chip analysis has demonstrated a significant difference in gene expression profiles between static and MG analog cultures of activated T cells. (Supported by NRA OLMSA-02 and NSCORT NAG5-4072 grants).