title: Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Pathology, Wake Forest School of Medicine , Winston-Salem, NC , USA.
authors: Ryne J
authors: RJ
authors: DeBo
authors: Thomas C
authors: TC
authors: Register
authors: David L
authors: DL
authors: Caudell
authors: Gregory D
authors: GD
authors: Sempowski
authors: Gregory
authors: G
authors: Dugan
authors: Shauna
authors: S
authors: Gray
authors: Kouros
authors: K
authors: Owzar
authors: Chen
authors: C
authors: Jiang
authors: J Daniel
authors: JD
authors: Bourland
authors: Nelson J
authors: NJ
authors: Chao
authors: J Mark
authors: JM
authors: Cline
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D008252:Macaca fascicularis; D008264:Macrophages / Q000276:immunology / Q000528:radiation effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Radiation; acute effects; cytokines; immunology; macrophage; molecular profiling; non-human primate; total body irradiation