The Effects of Low-dose Ionizing Radiation in the Activated Rat Basophilic Leukemia (RBL-2H3) Mast Cells*

Background: The effect of ionizing radiation in mast cells is not well known. Results: Low-dose ionizing radiation that did not induce cell toxicity inhibited mediator release through the suppression of receptor expression. Conclusion: Low-dose ionizing radiation regulates mast cell activation. Significance: This is the first evidence of the effect of low-dose radiation in the activated mast cell. Mast cells play important roles in many biological responses, such as those during allergic diseases and inflammatory disorders. Although laser and UV irradiation have immunosuppressive effects on inflammatory diseases by suppressing mast cells, little is known about the effects of γ-ionizing radiation on mast cells. In this study, we investigated the effects of γ-ionizing radiation on RBL-2H3 cells, a convenient model system for studying regulated secretion by mast cells. Low-dose radiation (<0.1 gray (Gy)) did not induce cell death, but high-dose radiation (>0.5 Gy) induced apoptosis. Low-dose ionizing radiation significantly suppressed the release of mediators (histamine, β-hexosaminidase, IL-4, and tumor necrosis factor-α) from immunoglobulin E (IgE)-sensitized RBL-2H3 cells. To determine the mechanism of mediator release inhibition by ionizing radiation, we examined the activation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, PKCs, and MAPK, and intracellular free calcium concentrations ([Ca2+]i). The phosphorylation of signaling molecules following stimulation of high-affinity IgE receptor I (FcϵRI) was specifically inhibited by low-dose ionizing radiation (0.01 Gy). These results were due to the suppression of FcϵRI expression by the low-dose ionizing radiation. Therefore, low-dose ionizing radiation (0.01 Gy) may function as a novel inhibitor of mast cell activation.