Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy of gamma-tocotrienol, a promising radiation countermeasure

Shilpa Kulkarni, Pankaj K. Singh, Sanchita P. Ghosh, Ana Posarac, Vijay K. Singh

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

This study aimed to determine the role of granulocyte colony-stimulating factor (G-CSF), induced by a promising radiation countermeasure, gamma tocotrienol (GT3), in protecting mice from lethal doses of ionizing radiation. CD2F1 mice were injected with an optimal dose of GT3 and a G-CSF antibody, and their 30-d survival was monitored. An appropriate antibody isotype was used as a control. Multiplex Luminex was used to analyze GT3-induced cytokines. G-CSF neutralization by exogenous administration of a G-CSF antibody was confirmed by analyzing serum cytokine levels. Our results demonstrate that GT3 significantly protected mice against ionizing radiation, and induced high levels of G-CSF in peripheral blood 24. h after administration. Injection of a G-CSF neutralizing antibody to the GT3-treated mice resulted in complete neutralization of G-CSF and abrogation of its protective efficacy. Administration of a G-CSF antibody did not affect levels of other cytokines induced by GT3. Histopathology of bone marrow from GT3-treated and -irradiated mice demonstrated protection of the hematopoietic tissue, and also that such protection was abrogated by administering a G-CSF antibody. Our results suggest that induction of high levels of G-CSF by GT3 administration is responsible for its protective efficacy against radiation injury.

Original languageEnglish (US)
Pages (from-to)278-285
Number of pages8
JournalCytokine
Volume62
Issue number2
DOIs
StatePublished - May 1 2013

Keywords

  • Gamma radiation
  • Gamma tocotrienol
  • Hematopoietic tissue
  • Mice
  • Radioprotection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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