title: α-Tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation-induced gastrointestinal injury in mice.
abstract: The goal of this study was to elucidate the role of α-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating the ionizing-radiation-induced gastrointestinal syndrome in mice. We demonstrate the efficacy of a bridging therapy that will allow the lymphohematopoietic system of severely immunocompromised victims exposed to ionizing radiation to recover from high doses of radiation. CD2F1 mice were irradiated with a high dose of radiation causing gastrointestinal syndrome (11 Gy, cobalt-60 γ-radiation) and then transfused intravenously (retro-orbital sinus) with whole blood or peripheral blood mononuclear cells (PBMC) from TS- and AMD3100-injected mice 2, 24, or 48 hours post irradiation and monitored for 30-day survival. Jejunum sections were analyzed for tissue area, surviving crypts, villi, mitotic figures, and basal lamina enterocytes. Our results demonstrate that infusion of whole blood or PBMC from TS- and AMD3100-injected mice significantly improved survival of mice receiving a high dose of radiation. Histopathology and immunostaining of jejunum from irradiated and TS- and AMD3100-mobilized PBMC-transfused mice reveal significant protection of gastrointestinal tissue from radiation injury. We demonstrate that TS and AMD3100 mobilize progenitors into peripheral circulation and that the infusion of mobilized progenitor-containing blood or PBMC acts as a bridging therapy for immune-system recovery in mice exposed to high, potentially fatal, doses of ionizing radiation.
authors.affiliation: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889-5603, USA. singh@afrri.usuhs.mil
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Wise
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Singh
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ducey
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seed
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001596:Benzylamines; D001773:Blood Cells / Q000637:transplantation*; D000080027:Cyclams; D000069585:Filgrastim; D005720:Gamma Rays / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000601:surgery; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000528:radiation effects / Q000648:ultrastructure; D007583:Jejunum / Q000473:pathology / Q000528:radiation effects; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D051379:Mice; D011828:Radiation Chimera; D011832:Radiation Injuries / Q000601:surgery*; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D024502:alpha-Tocopherol; D000069585:Filgrastim; C088327:plerixafor