Effects of gamma radiation on FcepsilonRI and TLR-mediated mast cell activation.

Radiation Biology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
The Journal of Immunology (Impact Factor: 5.36). 10/2007; 179(5):3276-86.
Source: PubMed

ABSTRACT Ionizing gamma radiation has several therapeutic indications including bone marrow transplantation and tumor ablation. Among immune cells, susceptibility of lymphocytes to gamma radiation is well known. However, there is little information on the effects of gamma radiation on mast cells, which are important in both innate and acquired immunity. Previous studies have suggested that mast cells may release histamine in response to high doses of gamma radiation, whereas other reports suggest that mast cells are relatively radioresistant. No strong link has been established between gamma radiation and its effect on mast cell survival and activation. We examined both human and murine mast cell survival and activation, including mechanisms related to innate and acquired immune responses following gamma radiation. Data revealed that human and murine mast cells were resistant to gamma radiation-induced cytotoxicity and, importantly, that irradiation did not directly induce beta-hexosaminidase release. Instead, a transient attenuation of IgE-mediated beta-hexosaminidase release and cytokine production was observed which appeared to be the result of reactive oxygen species formation after irradiation. Mast cells retained the ability to phagocytose Escherichia coli particles and respond to TLR ligands as measured by cytokine production after irradiation. In vivo, there was no decrease in mast cell numbers in skin of irradiated mice. Additionally, mast cells retained the ability to respond to Ag in vivo as measured by passive cutaneous anaphylaxis in mice after irradiation. Mast cells are thus resistant to the cytotoxic effects and alterations in function after irradiation and, despite a transient inhibition, ultimately respond to innate and acquired immune activation signals.

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    • "This coupled with immunoadjuvants such as TLRs, other innate immune receptor activators or cytokines can augment anti-tumor immunity (reviewed in Ma et al., 2011). In contrast to other immune cells, mast cells are relatively radioresistant (Soule et al., 2007). Mast cells have a slow rate of cell division, which will likely also make them more resistant to several common classes of chemotherapeutic drugs than rapidly dividing immune cells. "
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