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

• Type of Material: Article
• Authors: Jenine K. Sanzari, University of Pennsylvania; Ana L. Romero-Weaver, University of Pennsylvania; Gabrielle James, University of Pennsylvania; Gabriel Krigsfeld, University of Pennsylvania; Liyong Lin, Emory University; Eric S. Diffenderfer, University of Pennsylvania; Ann R. Kennedy, University of Pennsylvania
• Language: English
• Date: 2013-08-14
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Sanzari et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0071757
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 8
• Start Page: e71757
• End Page: e71757
• Grant/Funding Information: This research was supported by the NIH Radiation Biology Training Grant 2T32CAO9677 and the National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) grant.; The NSBRI is funded through the National Aeronautics and Space Administration (NASA) Class Code (NCC) 9–58.
• Keywords: IMMUNE-SYSTEM; BODY IRRADIATION; Multidisciplinary Sciences; Science & Technology - Other Topics; IONIZING-RADIATION; RESPONSES; Science & Technology; SPACEFLIGHT CONDITIONS; SPACE-FLIGHT; T-CELL-ACTIVATION; MICE; DOSE-RATE; HINDLIMB-UNLOADING MODEL
• Research Categories: Health Sciences, Oncology; Health Sciences, Radiology

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.