title: Kinetics of neutrophils in mice exposed to radiation and/or granulocyte colony-stimulating factor treatment.
abstract: Astronauts have the potential to develop the hematopoietic syndrome as a result of exposure to radiation from a solar particle event (SPE) during exploration class missions. This syndrome is characterized by a reduction in the number of circulating blood cells (cytopenias). In the present study the effects of SPE-like proton and γ radiation on the kinetics of circulating neutrophils were evaluated during a one-month time period using mice as a model system. The results revealed that exposure to a 2 Gy dose of either SPE-like proton or γ radiation significantly decreased the number of circulating neutrophils, with two nadirs observed on day 4 and day 16 postirradiation. Low circulating neutrophil count (neutropenia) is particularly important because it can increase the risk of astronauts developing infections, which can compromise the success of the mission. Thus, two granulocyte colony-stimulating factors (G-CSFs), filgrastim and pegfilgrastim were evaluated as countermeasures for this endpoint. Both forms of G-CSF significantly increased neutrophil counts in irradiated mice, however, the effect of pegfilgrastim was more potent and lasted longer than filgrastim. Using the expression of CD11b, CD18 and the production of reactive oxygen species (ROS) as markers of neutrophil activation, it was determined that the neutrophils in the irradiated mice treated with pegfilgrastim were physiologically active. Thus, these results suggest that pegfilgrastim could be a potential countermeasure for the reduced number of circulating neutrophils in irradiated animals.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Romero-Weaver
authors.forename: X S
authors.initials: XS
authors.lastname: Wan
authors.forename: E S
authors.initials: ES
authors.lastname: Diffenderfer
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D000069585:Filgrastim; D005720:Gamma Rays / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D007958:Leukocyte Count; D051379:Mice; D008813:Mice, Inbred ICR; D038042:Myelopoiesis / Q000528:radiation effects*; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000528:radiation effects; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects*; D011092:Polyethylene Glycols; D011522:Protons / Q000009:adverse effects*; D011833:Radiation Injuries, Experimental / Q000097:blood*; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012062:Relative Biological Effectiveness; D019445:Solar Activity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D011522:Protons; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D013755:Tetradecanoylphorbol Acetate; D000069585:Filgrastim