Abstract
Rationale
Natural killer (NK) cells play an important role in both the innate and adaptive arms of the immune system. While previous studies have demonstrated the effects of ionizing radiation on cytotoxic function of NK cells, little is known about how a chronic exposure to high LET alpha particles emitted by radionuclides will affect both NK population size and function. This study was conducted to determine the effects of 223RaCl2 on splenic NK cell population size and function in Swiss Webster mice.
Methods
Swiss Webster mice were administered intravenously with 0, 50, or 600 kBq/kg 223RaCl2. Spleens were harvested at 5, 12, and 19 days post-administration. The numbers of splenocytes per spleen were enumerated and flow cytometry was used to assess changes in the distribution of splenocyte subpopulations of B, CD4 and CD8 T lymphocytes, and NK cells. NK functional activity was quantified using YAC-1 target cells and the 51Cr-release assay.
Results
The total number of splenocytes was unaffected by 223RaCl2. However, significant changes in the distribution of splenocyte subpopulations were observed for NK cells and CD8 T lymphocytes. NK functional activity was enhanced substantially relative to controls at 12 days post-administration, but decreased markedly by day 19.
Conclusion
NK functional activity is both diminished and enhanced by 223RaCl2 depending on both administered activity and time post-administration. These results suggest that there may be an optimum window of time to combine the 223RaCl2-induced antitumor NK cell response with other cancer therapies that elicit immune activation.
Acknowledgments
The authors thank the NJMS Flow Cytometry Core for their tireless maintenance and troubleshooting assistance for matters pertaining to their instruments and the data generated thereof.
Disclosure statement
This study was supported in part by Grant 1R01CA198073 from the NIH, and New Jersey Commission on Cancer Research Pre-doctoral Fellowship Grant #DFHS15PPC009 (CNL). No other potential conflicts of interest relevant to this article exist.
Additional information
Funding
Notes on contributors
Calvin N. Leung
Calvin N. Leung is an MD PhD student at Rutgers New Jersey Medical School and Rutgers School of Graduate Studies, Newark, NJ, USA.
Donna M. Howell
Donna M. Howell, Ph.D., is Acting Dean and Chair of Natural Sciences at Middlesex College, Edison, NJ, USA, and Adjunct Professor at Rutgers New Jersey Medical School.
Roger W. Howell
Roger W. Howell, Ph.D., is Distinguished Professor at Rutgers New Jersey Medical School and Robert Wood Johnson Medical School, New Brunswick, NJ, USA.