Low to moderate dose 137 Cs (γ) radiation enhances M2 type macrophages function at short term associated with reduced inflammation at long term exposure in ApoE (-/-) mice

Abstract

Effects of low doses of ionizing radiation on atherosclerosis are still a source of many uncertainties, and in particular whether these effects generate anti or pro-inflammatory responses. Furthermore, the delay of occurrence of such effects upon irradiation are unknown. Atheroprone ApoE(−/−) mice were exposed to single doses of 0, 0.05, 0.5 and 1 Gy of 137Cs (γ) at 10.35 mGy.min− 1 dose rate. Short term (24 hours) effects on bone marrow-derived macrophage polarization and long term (100 days) consequences on atherosclerotic plaques were investigated. We found a significant dose-dependent increase of Chil3 and Retnla anti-inflammatory markers gene expression in M0 and M2 type macrophages upon 24 hours exposure and no effects on M1 types. These effects were associated with a dose-dependent increase of IL-10 and a reduction of IL-1beta secretions in M0 and M2 and an increase of IL-6 in M1 type macrophages. Circulating pro-inflammatory Ly6CHigh monocytes were reduced at 24 hours and anti-inflammatory Ly6Clow monocytes were notably increased in the spleen 100 days upon irradiation. Long term exposures to any doses did not affect atherosclerotic plaque size determined by OilredO. However, a tendency in plaque stability, determined by collagen and alpha-smooth muscle actin increase was observed, associated with a significant reduction of plaque macrophage content at 1Gy. Taking together these findings show an increase of anti-inflammatory behavior of M2 macrophages with low to moderate doses of ionizing radiation at short term after irradiation, at long term these changes could influence atheromatous plaques after irradiation with decreased macrophages contents. These results suggest that the mechanisms that lead to on atheroprotective response after low and moderate doses of ionizing radiation would involve early effects on circulating monocytes and the macrophages polarization towards an anti-inflammatory profile.