Leukocyte activity is altered in a ground based murine model of microgravity and proton radiation exposure
Open accessAbstract
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.
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In a mouse model, T-cells did not become activated following exposure to low doses of SPE-like proton radiation, and the animals were susceptible to a non-toxic bacterial challenge of organisms (Pseudomonas aeruginosa, Klebsiella pneumoniae) that are relatively innocuous and ubiquitous on Earth and have been detected aboard the ISS.
“In a mouse model, T-cells did not become activated following exposure to low doses of SPE-like proton radiation, and the animals were susceptible to a non-toxic bacterial challenge of organisms (Pseudomonas aeruginosa, Klebsiella pneumoniae) that are relatively innocuous and ubiquitous on Earth and have been detected aboard the ISS [65,66].”
From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [65]
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References 46 · Cited by 47
- Authors
- Sanzari, J. K., Romero-Weaver, A. L., James, G., Krigsfeld, G., Lin, L., Diffenderfer, E. S., & Kennedy, A. R.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Kennedy, Ann R.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-08-14
- Volume
- 8
- Issue
- 8
- Pages
- e71757
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3743739
- OpenAlex
- W2004957459
- Cited by
- 47
- References
- 46
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 6 · 2016: 2 · 2015: 7 · 2014: 10 · 2013: 1
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Aeronautics and Space Administration
- National Space Biomedical Research Institute
- National Institutes of Health
- U.S. Public Health Service (2T32CAO9677)
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- simulated microgravity, proton radiation, hindlimb unloading, leukocyte function, lymphocyte subsets, T cell activation, CD69, T cell proliferation, splenocytes, space medicine, hematopoietic cells
- MeSH terms
- Animals, Humans, Immunity, Cellular, Lymphocyte Activation, Radiation Injuries, Experimental, Space Flight, Spleen, T-Lymphocytes, Cytotoxic, Weightlessness Simulation, Astronauts, Lymphocyte Count, Hindlimb Suspension, Cell Proliferation, Mice
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