The combined effects of reduced weightbearing and ionizing radiation on splenic lymphocyte population and function

Abstract

Purpose The effects of radiation +/− hypogravity on immunologic function were investigated using the Partial Weight Suspension (PWS) model (Wagner et al. 2010). Materials and methods Mice were exposed to 0.5, 1, or 2 Gray (Gy) dose of gamma radiation and then placed in the PWS system for 4, 24, 48 hours, or 4 days. Spleens were excised and white blood cells were prepared for flow cytometry analyses. Results The combination of PWS + radiation (1 and 2 Gy doses only) resulted in decreased cell viability at the 24 h (~16% decrease), 48 h (~20% decrease), and 4 day (~20% decrease) time points, compared to the PWS (no radiation) and no treatment (non-suspended, non-irradiated) groups. The T lymphocyte (thymus-derived) population increased by ~10% (24 h, 48 h, and 4 day time points), while the B lymphocyte (bursal or bone marrow-derived) population decreased by ~10% (at all time points examined), when mice were exposed to PWS + radiation (2 Gy dose only), compared to the PWS or no treatment groups. T cell activation was observed in the PWS group and the 0.5 Gy +/− PWS groups at the 4 and 24 h time points, compared to the no treatment group. However, T cell activation was significantly suppressed (~85%) at the acute time points in the 2 Gy +/− PWS groups, comparable to the no treatment group. Conclusions Ionizing radiation in the absence and presence of simulated hypogravity results in acute lymphocyte dysfunction and compromised immune response.

Biological effects of space radiation and development of effective countermeasures

“…In contrast, simulated hypogravity brought about by PWS was shown to potentiate splenic lymphocytes to the cell killing effects of radiation (136). A number of other studies indicated that SPE radiation and simulated microgravity produced by HS led to synergistic adverse effects on hematopoietic and immune cell functions, including bacterial containment in the GI tract (152), T-cell activation (136, 138), and death from a bacterial challenge at a sub-lethal dose (151). …”

“…To evaluate the impact of hypogravity on the effect of SPE radiation on immunological function, experiments were performed with 6–8 week old female ICR mice that were irradiated with 0.5, 1 or 2 Gy of γ-rays with or without hypogravity simulated using the PWS model, described by Wagner et al (149). The combination treatment with PWS and γ-ray irradiation decreased total splenic lymphocyte viability in a dose dependent manner, and the suppressed splenic lymphocyte viability in groups exposed to a 2 Gy dose of radiation persisted for 4 days, which was the last time point evaluated in the study (136). In addition, the viability of splenic lymphocytes was significantly lower in the mice that received a 1 Gy dose of γ-rays in combination of PWS treatment than in the mice that received a 1 Gy dose of γ-rays without PWS treatment on Day-1 or Day 4 post-irradiation.…”

“…The changes in peripheral leukocytes in animals post-irradiation have been evaluated in ICR mice irradiated with 225-kVp X-rays (132), γ-rays from 60 Co (133) or 137 Cs (134–136), protons with energies of 50-MeV (133), 51-MeV (137), 70-MeV (133), 74-MeV (134, 135), 78.4 MeV (138) and 1-GeV protons (137, 139) as well as protons with eight different energies between 31 and 75 MeV and simulated SPE protons with energies between 30 and 150 MeV (140). The changes in peripheral leukocytes have also been examined in ferrets irradiated with 60 Co or 137 Cs γ-rays and 110-MeV protons (141, 142) and Yucatan minipigs irradiated with 6-MeV electrons (130), 6+12-MeV electrons and SPE protons (143, 144).…”

“…The other immunological issue of great importance to the space program is the observation of additive or synergistic synergism in adverse effects caused by SPE radiation exposure and simulated microgravity conditions; interactive effects between SPE radiation and simulated microgravity have been observed for various immunological parameters at doses of radiation that could be received by astronauts during space travel [e.g., (136, 138, 151, 152)]. The results indicate that, under simulated microgravity conditions, the effects of a given dose of SPE radiation can be considerably more severe than the effects observed for the same dose of radiation in normal, control animals.…”

Are biological effects of space radiation really altered under the microgravity environment?

“…As examples, interesting studies on IR effects under MMG or PWS, reported recently, are introduced below. Sanzari et al (2011) investigated the effects of radiation plus/minus hypogravity on immunologic function using the PWS model established by Wagner et al (2010). Mice were exposed to γ -rays with a dose of 0.5, 1, or 2 Gy and were then placed in the PWS system for 4, 24, 48, or 96 h. The combination of PWS plus γ -rays (1 or 2 Gy) resulted in an approximate 20% decrease in cell viability of lymphocytes after 24, 48, or 96 h, compared with those treated with PWS, which itself did not significantly change the level of cell viability.…”