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Introduction: Exposure to the microgravity environment could cause human physiological abnormalities that include fluid shift, anemia, osteoporosis, immunosuppression, etc. Monocytes and macrophages are important components of the immune system and could serve as precursors of osteoclasts. A direct effect of microgravity on monocytes and/or macrophages may contribute to immunosuppression and osteoporosis. Methods: To test this hypothesis, we reviewed the studies concerning the direct effects of microgravity on the monocyte/macrophage physiology and discussed the links of these effects to the human physiological abnormalities caused by microgravity. Results: Inhibited development and proliferation, reduced production of reactive oxygen species and proinflammatory cytokines and inhibited cell locomotion were observed in monocyte/macrophages under microgravity. These microgravity effects may lead to immunosuppression. Enhanced osteoclastogenesis was observed in monocyte/macrophages under microgravity. This microgravity effect may lead to osteoporosis. The molecular mechanisms underlying these microgravity effects were also presented. For example, the mechanisms of the inhibited cell locomotion under microgravity include: reduced β-actin expression, abnormality in the structure of focal adhesions and impaired protein kinase C signaling. Conclusion: The elucidation of the molecular mechanisms by which microgravity interferes with the monocyte/macrophage physiology may favor the identification of potential drug targets to reverse the deleterious effects of microgravity. Furthermore, due to the fact that macrophages are professional antigen-presenting cells, we propose that microgravity might modulate the efficacy of antigen presentation by macrophages in the immune response to vaccines.

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