Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.

Published

Journal Article

PURPOSE: The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques. MATERIALS AND METHODS: Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses. RESULTS: Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP-1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals. CONCLUSIONS: Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation.

Full Text

Duke Authors

Cited Authors

  • DeBo, RJ; Register, TC; Caudell, DL; Sempowski, GD; Dugan, G; Gray, S; Owzar, K; Jiang, C; Bourland, JD; Chao, NJ; Cline, JM

Published Date

  • June 2015

Published In

Volume / Issue

  • 91 / 6

Start / End Page

  • 510 - 518

PubMed ID

  • 25786585

Pubmed Central ID

  • 25786585

Electronic International Standard Serial Number (EISSN)

  • 1362-3095

Digital Object Identifier (DOI)

  • 10.3109/09553002.2015.1028597

Language

  • eng

Conference Location

  • England