title: Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy of gamma-tocotrienol, a promising radiation countermeasure.
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 24h 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.
authors.affiliation: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of Health Sciences, Bethesda, MD 20889-5603, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Singh
authors.forename: Sanchita P
authors.initials: SP
authors.lastname: Ghosh
authors.forename: Ana
authors.initials: A
authors.lastname: Posarac
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D057134:Antibodies, Neutralizing; D002839:Chromans / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000276:immunology*; D008297:Male; D051379:Mice; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000906:Antibodies; D057134:Antibodies, Neutralizing; D002839:Chromans; D011837:Radiation-Protective Agents; D014810:Vitamin E; D016179:Granulocyte Colony-Stimulating Factor; C013649:plastochromanol 8