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

  • Academic Journal
  • DeBo RJ; Department of Pathology, Wake Forest School of Medicine , Winston-Salem, NC , USA.
    Register TC
    Caudell DL
    Sempowski GD
    Dugan G
    Gray S
    Owzar K
    Jiang C
    Bourland JD
    Chao NJ
    Cline JM
  • International journal of radiation biology [Int J Radiat Biol] 2015 Jun; Vol. 91 (6), pp. 510-8. Date of Electronic Publication: 2015 Apr 22.
  • English
  • 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.
Additional Information
Publisher: Taylor & Francis Country of Publication: England NLM ID: 8809243 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1362-3095 (Electronic) Linking ISSN: 09553002 NLM ISO Abbreviation: Int J Radiat Biol Subsets: MEDLINE
Original Publication: London ; New York : Taylor & Francis, [c1988-
Radiation Injuries, Experimental/*genetics
Radiation Injuries, Experimental/*immunology
Whole-Body Irradiation/*adverse effects
Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Chemokine CCL2/blood ; Dose-Response Relationship, Radiation ; Female ; Gene Expression Profiling ; Lymphoid Tissue/immunology ; Lymphoid Tissue/pathology ; Lymphoid Tissue/radiation effects ; Macaca fascicularis ; Macrophages/immunology ; Macrophages/radiation effects ; Ovariectomy ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Radiation Injuries, Experimental/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/radiation effects
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U19 AI067798 United States AI NIAID NIH HHS; UC6 AI058607 United States AI NIAID NIH HHS
Keywords: Radiation; acute effects; cytokines; immunology; macrophage; molecular profiling; non-human primate; total body irradiation
0 (Antigens, CD)
0 (Antigens, Differentiation, Myelomonocytic)
0 (CD68 antigen, human)
0 (Chemokine CCL2)
0 (RNA, Messenger)
Date Created: 20150320 Date Completed: 20150804 Latest Revision: 20181113
20221216
PMC4566160
10.3109/09553002.2015.1028597
25786585
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