The influence of leptin on the activity of lung lymphocytes under simulated microgravity

Exposure to microgravity has been implicated in the compromised immune function in space travellers, resulting in opportunistic infections, poor wound healing, and cancer. Since recent studies have suggested that leptin was capable of modulating immune responses, the purpose of this study was to examine effects of microgravity on the activation and proliferation of rat lung lymphocytes and then to examine the effects of leptin-mediated signal transduction mechanisms of lymphocyte activation in these same conditions. In control conditions (T-flasks cultured cells) leptin was not able by itself to increase lymphocytes proliferation, or induce significant increase of either IL-2 production or expression of lymphocytes activation markers, such as CD25 and CD71, while it markedly enhanced the positive effects induced on these parameters by concanavalin A (ConA). Using clinostatic rotating wall vessel (RWV) bioreactors to simulate a microgravity environment, we found that ConA responsiveness was inhibited. Moreover, under these conditions, leptin was not able to reverse these impaired functions. Accordingly with the above cited inhibitory effects exerted by the simulated microgravity environment, evidence was also obtained of defects in lymphocyte intracellular signal transduction induced by the incubation in RWV bioreactors, namely concerning decreased ConA-mediated PKC activity, and reduced expression of NF-κB, c-fos, and ERK1/2. Again, leptin appeared to be unable in restoring a physiologic increase of these parameters, different from what could be observed after complementation of the ConA-mediated signalling with phorbol myristate acetate, which instead demonstrated to overcome the inhibition of lymphocytes activating functions, in the presence of simulated microgravity conditions.