Effect of CCL1 antisense ODN on bacterial translocation in mice irradiated with whole body 137Cs γ-rays: elimination of M2b macrophages in translocation sites (111.19)

Abstract

Abstract Mice irradiated with 5 Gy whole body 137Cs γ-rays (WBI-mice) are shown to be carriers of M2bMϕ (IL-10+CCL1+LIGHT+IL-12- Mϕ), which are inhibitory on the host antibacterial innate immunities in bacterial translocation. M2bMϕ maintain their suppressor cell properties through the production of CCL1. In this study, therefore, we tried to eliminate M2bMϕ from mesenteric lymph nodes (MLN) of WBI-mice by CCL1 antisense ODN gene therapy. WBI-mice were treated with CCL1 antisense ODN with various doses (2, 10, 50, or 250 μg/mouse), routes (i.p., i.m. or s.c.) and schedules (twice a day for 2 to 7 days, starting 1 to 4 weeks after γ-irradiation). F4/80+ MLN-Mϕ isolated from these mice were identified as M2bMϕ by their abilities to express intracellular IL-10 and LIGHT mRNA. As a control, MLN-Mϕ were isolated from WBI-mice treated with scrambled ODN and subjected to the same test. In the results, the numbers of MLN-M2bMϕ were greatly reduced in WBI-mice treated s.c. with 10 to 50 μg/mouse of CCL1 antisense ODN twice a day for 2 days, 5 days or 7 days, started 1 to 3 weeks after γ-irradiation. However, MLN-M2bMϕ were detected in WBI-mice treated with CCL1 antisense ODN twice a day for 2 days started 4 weeks after the irradiation. These results indicate that M2bMϕ are eliminated from MLN of WBI-mice s.c. treated with CCL1 antisense ODN twice a day for 2 days starting 1 to 3 weeks after γ-irradiation.