Leukocyte Activity Is Altered in a Ground Based Murine Model of Microgravity and Proton Radiation Exposure

Abstract

Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU) model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose) and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC), lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure) result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and simulated microgravity effects on hematopoietic, specifically immune cells.

Biological effects of space radiation and development of effective countermeasures

“…In addition, results from these studies indicated that T cell activation was decreased in the irradiated mice (1 or 2 Gy) with or without simulated hypogravity (PWS). Similar results were observed in experiments using mice exposed to SPE-like proton radiation with and without simulated hypogravity produced by HS (134, 138). In these experiments, mice were suspended prior to and after SPE proton radiation exposure and total leukocyte numbers and splenic lymphocyte functions were evaluated on days 4 or 21 after the radiation exposure with and without HS.…”

“…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).…”

“…Numerous studies have been performed to evaluate the effects of SPE radiation on the immune system as a part of research on the acute risks of SPE radiation exposure (138, 144,148, 151, 152). Many of the SPE radiation studies were performed with and without microgravity simulated with PWS or HS (134, 138,148, 151–153).…”

“…Many of the SPE radiation studies were performed with and without microgravity simulated with PWS or HS (134, 138,148, 151–153). For the studies related to immune system effects, mice were exposed to homogeneous doses of either γ-ray or SPE- like proton radiation.…”

Acute effects of solar particle event radiation

“…(v) T-cell activation was reduced in mice exposed to SPE-like radiation with or without simulated hypogravity (either partial weight suspension or hindlimb suspension) (e.g. [4]). (vi) Radiation and simulated hypogravity had synergistic effects on immune system biological endpoints (e.g.…”