γ-Ray-associated XBP-1+ macrophages as an inducer of M2 macrophages (117.3)

Abstract

Abstract The susceptibility of mice to infections with opportunistic pathogens is strongly influenced by M2MΦ appeared in association with whole body γ-irradiation. Therefore, in this study, we investigated why M2MΦ were predominantly generated in mice exposed to whole body γ-irradiation. F4/80+ MΦ were isolated from peritoneal exudates of mice 6-24 h after 5 Gy of γ-irradiation. The expressions of XBP-1 in these MΦ preparations were detected by Western Blot. The production and intracellular CCL2 expression by XBP-1+ MΦ were assayed by ELISA and flow cytometry. In some experiments, resident MΦ were cultured with media supplemented with culture fluids of XBP-1+ MΦ (33%, v/v). MΦ with the ability to produce IL-10 and not produce IL-12 were considered as M2MΦ. In the results, XBP-1+ MΦ were demonstrated in peritoneal MΦ preparations isolated from mice irradiated with 5 Gy of γ-rays. CCL2 was detected in culture fluids of XBP-1+ MΦ. Also, intracellular CCL2 was detected in XBP-1+ MΦ by flow cytometry. The conversion of MΦ from resident MΦ to M2MΦ was demonstrated when resident MΦ were cultured with media supplemented with the culture fluids of XBP-1+ MΦ. Resident MΦ did not change to M2MΦ when they were cultured with XBP-1+ MΦ culture fluids previously depleted of CCL2. These results indicate that the MΦ conversion from resident MΦ to M2MΦ is stimulated by CCL2 released from XBP-1+ MΦ that appear in association with whole body γ-irradiation.