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Exp Hematol. 2012 May;40(5):407-17. doi: 10.1016/j.exphem.2012.01.005. Epub 2012 Jan 10.

α-Tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation-induced gastrointestinal injury in mice.

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  • 1Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889-5603, USA. singh@afrri.usuhs.mil

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.

Published by Elsevier Inc.

PMID:
22240608
[PubMed - indexed for MEDLINE]
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