Effect of microgravity on living system

–Our planet Earth has been proliferating with life for billion years and life has survived in the constant influence ofgravity. So it’s a major question if the gravity has an influence over the major processes and mechanisms of earth-inhabiting organisms and the environment. Ever since the first space missions and many ground-based experiments, it is a well-established fact now thatthe immune cell function is severely suppressed in 0g, which makes the cells of the immune system a noble model organism to investigate the influence of gravity on life at the cellular and molecular level. Also, it has been previously found that osteoblast growth is reduced in microgravity and the ability to be activated to grow is significantly changed during a spaceflight. The studies have suggested that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may prove to be a significant factor in bone loss during a spaceflight. Thus, by understanding the impact of gravity on cellular functions on Earth one can conclude not only important information about role of gravity on the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with problems relating to immune system and its defence mechanisms during space exploration. In this paper, I review the knowledge about the question i.e. if and how cellular signal transduction pathways in the cells of immune system depends on the existence of gravity and how gravity plays a role in bone growth, that has been perceived till date. I. CHANGED IMMUNE RESPONSES IN SPACE The first report about disturbed immune response that was obtained in 70s indicated reduced activity of blood lymphoid cells discovered in crew members of Soyuz, Apollo and Skylab spaceships [1, 2]. A virus, Varicella zoster which stays latent after the primary infection but gets activated in organisms with a suppressed immune system such as in patients having AIDS or cancer, has been reported to become sub clinically active in astronauts [3, 4]. Also, it is well known that gravity can be perceived by gravireceptors that is a statocyst-like organelles or gravisensitive ion channels in the cell membrane. Although in unicellular organisms in which gravisensitivity plays an important role in signal transduction and cell behaviour [5, 6] for example in Paramecium or loxodes, the mechanisms of these processes are still not properly known but further studies and research work is in progress.It is well known that proliferative response of T lymphocytes after mitogenic stimulation is strongly supressed when in microgravity after the pioneering discovery of Cogoli et al almost 20 years ago in a space lab mission [7, 8]. Gravitational unloading: Changes observed in lymphocytes Before getting onto the changes observed in T lymphocytes attributed to gravitational unloading, a clear distinction must be made between two kinds of experiments: (i) In vitro experiments conducted with cells purified from the peripheral blood of test subjects obtained before flight and then exposed inflight to mitogens and other activators, and (ii) Ex vivo experiments conducted with lymphocytes obtained from crew members of space missions exposed to mitogens prior to and after space flight [8]. Where the first approach can be considered as a basic research in cell biology in space; the second one is an approach to identify the effects of the stress of spaceflight on the immune response of astronauts. The data and results obtained from in vitro experiments have shown that lymphocyte activation is nearly totally suppressed in microgravity. This activation depression is confirmed by experiments conducted on Earth in the fast rotating clinostat. Apparently, when lymphocytes were cultured at 10 g in a centrifuge, activation increased. In microgravity cell adhesion might get reduced, thus partly accounting for fact that the cell activation is decreased which was confirmed later that the results were due to the simultaneous activation of Tand B-cells by concanavalinA. The reduced activation observed in lymphocytes from crewmembers of space missions can be attributed to both the physical and psychological stress of spaceflight. This observation was later confirmed by investigations on subjects undergoing stress on Earth [8]. Since the study of the function of immune cells in microgravity has been a major topic for research and studies for more than 20 years in various labs including the major ones like NASA. After several succeeding experiments it has become clear that the immune system is highly depressed in more than 50% of the astronauts during and after space flight. Also, a dramatic change was observed in the activation of T lymphocytes Effect of microgravity on living system 2 by mitogens in vitro. Cogoli et al conducted gravitational studies in Spacelab laboratory, in MIR station and in sounding rockets and on the ground in the clinostat and the centrifuge. The major experimental approaches to be included were: (i) Ex vivo studies conducted with blood samples taken from astronauts; (ii) in vivo studies based on the application of seven antigens to the skin of the astronauts; (iii) in vitro studies performed with immune cells taken from the blood of healthy donors (not astronauts). The data & results from these in vivo and ex vivo studies are in agreement with those of other laboratories and thus clearly show that the immune function is depressed in the majority i.e. 50% of astronauts due to the stress of space flight rather than by a direct influence of gravity on the cell. Thus one can say that Immune suppression may become a critical and severe hazard on flights of long duration on space stations or to other planets. Further, in vitro experiments show that a dramatic depression of activation is observed in the cultures of free-floating lymphocytes and monocytes by the mitogen concanavalin A, while on the other hand, when the cells are attached to micro carrier beads, activation is more than doubled. Therefore, such effects may be attributed to both direct and indirect effects of gravity or to be clearer, gravitational unloading on basic biological mechanisms of the cell. Although the in vitro data are very significant to clarify major aspects of the signal transduction of T cell activation, they are still not quite descriptive of the changes of the immune function of the astronauts [9]. Cell-to-Cell Communication and Signal Transduction is disturbed in microgravity. Several studies report alterations in signal transduction in lymphocytes. In lymphocytes, microgravity was found to be affecting the protein kinase C [11,12]. Although the delivery of first activation signal, patching and capping of conA-binding membrane proteins seemed to occurr normally in spaceflight [13]. These findings have suggested the existence of gravisensitive cellular targets upstream from PKC and downstream from the TCR/CD3. T cells were subjected to simulated microgravity provided by the random-positioning machine (RPM) and their DNA array analysis was done that revealed an alteration of several signal moduls, in particular NF-kB and MAPK-signalling [14]. Also the expression of the early oncogenes c-fos, c-myc and c-jun is found to be inhibited during spaceflight [15]. Impaired monocyte function: During the spacelab-mission SLS-1, monocytes were found to loose their capability of secreting IL-1 [16] and of expressing IL-2-receptor [26]. In gene induction associated with differentiation of monocytes into macrophages, examination of gene expression of monocytes under real microgravity demonstrated significant changes [18]. Kaur et al. [19] conducted a study in which he performed experiments on monocytes isolated from astronauts before and after a mission and then compared the results with control groups. They found a reduction of phagocytosis and also, a reduced oxidative burst and degranulation-capacity. Meloni et al. [20] recently demonstrated that simulated weightlessness leads to huge alterations in the cytoskeleton of monocytes, which in turn influences motility and also, recently revealed during Effect of microgravity on living system 3 an ISS experiment, a severe reduction in the locomotion ability of monocytic cells in microgravity [21]. Further studies with natural killer cells in simulated microgravity and in real microgravity on board of the ISS, revealed significant results; one of them being that neither cytotoxic effects nor interferon production is altered in microgravity [22]. Cell migration in microgravity Neutrophil locomotion is integral for immune effector function, because the cells have to leave the blood vessels and then navigate to places of infection and injury to fulfil their main task of phagocytosis thus making cell migration an important factor. They are one of the most important cells regulating the immune response, because they can, in several ways, influence both induction and the effector stage of immunological reactions. Several studies have provided evidence of a disturbed function of neutrophil granulocytes: Returning astronauts of spaceflight missions exhibited a strong increase of neutrophil granulocytes immediately after landing [23,24], and a 10-fold decrease was seen in neutrophil chemotactic assays showed in the optimal doseresponse after landing [25]. [Fig 1 Source: 59] Cell migration is an essential and must characteristic of life. Multicellular organisms must be motile to obtain nourishment, avoid being eaten in their own right and for their own good, respond to changes in environment and reproduce. In previous studies using simulated microgravity, an inhibition of lymphocyte locomotion was being demonstrated by changes in gravity demonstrated through type I collagen [26,27], and a decreased migration potential was observed in culture of human bone marrow CD34+ cells using NASA 's rotating wall vessels [28]. An altered movement in real mic