

Ana Lilian Romero-Weaver, Liyong Lin, Alejandro Carabe-Fernandez, Ann R Kennedy


Astronauts traveling in space missions outside of low earth orbit will be exposed for longer times to a microgravity environment. In addition, the increased travel time involved in exploration class missions will result in higher risks of exposure to significant doses of solar particle event (SPE) radiation. Both conditions could significantly affect the number of circulating blood cells. Therefore, it is critical to determine the combined effects of exposure to both microgravity and SPE radiation. Thus, the purpose of the present study was to assess the risk that astronauts would have in the event of exposure to SPE radiation by evaluating the effects of SPE-like proton radiation and/or simulated microgravity on circulating blood cells using mouse as the model system. The results indicate that exposure to HU alone caused minimal or no significant changes in mouse circulating blood cell numbers. The exposure of mice to the combined treatment with SPE-like proton radiation and HU caused a significant decrease in the number of circulating lymphocytes, granulocytes and platelets which was similar to the decrease caused by exposure to SPE-like proton radiation alone. The reduced numbers of circulating lymphocytes, granulocytes and platelets resulting from the combined exposure to SPE-like proton radiation and HU indicate that astronauts participating in exploration class missions are at higher risks of developing infections and thrombotic diseases; thus, countermeasures are necessary for these biological endpoints.


Allebban, Z., Ichiki, A.T., Gibson, L.A., Jones, J.B., Congdon, C.C., and Lange, R.D. 1994. Effects of spaceflight on the number of rat peripheral blood leukocytes and lymphocyte subsets. Journal of leukocyte biology. 55:209-213.

Aviles, H., Belay, T., Vance, M., and Sonnenfeld, G. 2005. Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading. Neuroimmunomodulation. 12:173-81.

Baqai, F.P., Gridley, D.S., Slater, J.M., Luo-Owen, X., Stodieck, L.S., Ferguson, V., Chapes, S.K., and Pecaut, M.J. 2009. Effects of spaceflight on innate immune function and antioxidant gene expression. J. of Applied Physiology. 106: 1935-1942.

Benschop, R.J., Rodriguez-Feuerhahn, M., and Schedlowski, M. 1996. Catecholamine-induced leukocytosis: early observations, current research, and future directions. Brain, behavior, and immunity. 10, 77-91.

Borchers, A.T., Keen, C.L., and Gershwin, M.E. 2002. Microgravity and immune responsiveness: implications for space travel. Nutrition. 18:889-898.

Chapes, S.K., Mastro, A.M., Sonnenfeld, G., and Berry, W.D. 1993. Antiorthostatic suspension as a model for the effects of spaceflight on the immune system. Journal of leukocyte biology. 54:227-235.

Dai, K., Wang, Y., Yan, R., Shi, Q., Wang, Z., Yuan, Y., Cheng, H., Li, S., Fan, Y., and Zhuang, F. 2009. Effects of microgravity and hypergravity on platelet functions. Thromb Haemost. 101:902-910.

Dainiak, N. 2002. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 30:513-528.

Fuse, A., Aoki, Y., Sato, T., Sunohara, M., and Takeoka, H. 2002. Decreased platelet level in peripheral blood of mice by microgravity. Uchu Seibutsu Kagaku. 16:159-60.

Gridley, D.S., Rizvi, A., Luo-Owen, X., Makinde, A.Y., Coutrakon, G.B., Koss, P., Slater, J.M., and Pecaut, M.J. 2008. Variable hematopoietic responses to acute photons, protons and simulated solar particle event protons. In Vivo. 22:159-169.

Grove, D.S., Piskhak, S.A., and Mastro, A.M. 1995. The effect of a 10 day space flight on the function, phenotype, and adhesion molecule expression of splenocytes and lymph node lymphocytes. Exp. Cell Res. 219: 102-109.

Hellweg, C.E., and Baumstark-Khan, C. 2007. Getting ready for the manned mission to Mars: the astronauts' risk from space radiation. Naturwissenschaften. 94, 517-526.

Ichiki, A.T., Gibson, L.A., Jago, T.L., Strickland, K.M., Johnson, D.L., Lange, R.D., and Allebban, Z. 1996. Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells. Journal of leukocyte biology. 60:37-43.

Kaur, I., Simons, E.R., Castro, V.A., Mark Ott, C., and Pierson, D.L. 2004. Changes in neutrophil functions in astronauts. Brain, behavior, and immunity. 18, 443-450.

Kaur, I., Simons, E.R., Castro, V.A., Ott, C.M., and Pierson, D.L. 2005. Changes in monocyte functions of astronauts. Brain, behavior, and immunity. 19:547-554.

Maks, C.J., Wan, X.S., Ware, J.H., Romero-Weaver, A.L., Sanzari, J.K., Wilson, J.M., Rightnar, S., Wroe, A.J., Koss, P., Gridley, D.S., Slater, J.M., and Kennedy, A.R. 2011. Analysis of white blood cell counts in mice after gamma- or proton-radiation exposure. Radiat Res. 176:170-176.

Mills, P.J., Meck, J.V., Waters, W.W., D'Aunno, D., and Ziegler, M.G. 2001. Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration. Psychosomatic medicine. 63:886-890.

Morey-Holton, E.R., and Globus, R.K. 2002. Hindlimb unloading rodent model: technical aspects. J Appl Physiol. 92:1367-1377.

Murdaca, G., Setti, M., Brenci, S., Fenoglio, D., Lantieri, P., Indiveri, F., and Puppo, F. 2003. Modifications of immunological and neuro-endocrine parameters induced by antiorthostatic bed-rest in human healthy volunteers. Minerva Med. 94:363-378.

O'Donnell, P.M., Orshal, J.M., Sen, D., Sonnenfeld, G., and Aviles, H.O. 2009. Effects of exposure of mice to hindlimb unloading on leukocyte subsets and sympathetic nervous system activity. Stress. 12:82-88.

Plett, P.A., Abonour, R., Frankovitz, S.M., and Orschell, C.M. 2004. Impact of modeled microgravity on migration, differentiation, and cell cycle control of primitive human hematopoietic progenitor cells. Exp Hematol. 32:773-781.

Romero-Weaver A.L., Wan X.S., Diffenderfer E.S., Lin L. and Kennedy A.R. 2013a. Effect of SPE-like Proton or Photon Radiation on the Kinetics of Mouse Peripheral Blood Cells and Radiation Biological Effectiveness Determinations. Astrobiology. 13:570-577.

Romero-Weaver A.L., Wan X.S., Diffenderfer E.S., Lin L., and Kennedy A.R. 2013b. Kinetics of Neutrophils in Mice Exposed to Radiation and/or Granulocyte Colony-Stimulating Factor Treatment. Radiat Res. 180:177-188.

Sanzari, J.K., Wilson, J.M., Wagner, E.B., and Kennedy, A.R. 2011. The combined effects of reduced weightbearing and ionizing radiation on splenic lymphocyte population and function. Int J Radiat Biol. 87:1033-1038.

Sanzari, J.K., Romero-Waver, A.L., James, G., Krigsfeld, G., Liyong, L., Diffenderfer, E.S., and Kennedy, A.R. 2013. Leukocyte activity is altered in a ground based murine model of microgravity and proton radiation exposure. PLoS One. 8:e71757.

Stowe, R.P., Sams, C.F., and Pierson, D.L. 2003. Effects of mission duration on neuroimmune responses in astronauts. Aviation, space, and environmental medicine. 74:1281-1284.

Wei, L.X., Zhou, J.N., Roberts, A.I., and Shi, Y.F. 2003. Lymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the spleen and thymus. Cell Res. 13:465-471.

Zhou, Y., Ni, H., Li, M., Sanzari, J.K., Diffenderfer, E.S., Lin, L., Kennedy, A.R., and Weissman, D. 2012. Effect of solar particle event radiation and hindlimb suspension on gastrointestinal tract bacterial translocation and immune activation. PLoS One. 7:e44329.

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