Effect of CCL1 antisense ODN on bacterial translocation in mice irradiated with whole body 137Cs γ-rays: induction of M1 macrophages in translocation sites (111.21)

Abstract

Abstract M1Mϕ (IL-10-IL-12+ Mϕ) in mesenteric lymph nodes (MLN) of mice have been identified as major effector cells in the host defense against enterococcal translocation and subsequent sepsis. However, M1Mϕ are not easily generated in 5 Gy whole body γ-irradiated mice (WBI-mice) whose M2bMϕ (IL-10+CCL1+LIGHT+IL-12- Mϕ) predominate. M2bMϕ are inhibitory on resident Mϕ conversion to M1Mϕ. In our previous studies, M2bMϕ were not demonstrated in MLN of WBI-mice treated with CCL1 antisense ODN. In this study, therefore, we tried to induce M1Mϕ by enterococcal antigen in MLN of WBI-mice treated with CCL1 antisense ODN. WBI-mice were treated s.c. with CCL1 antisense ODN (10 μg/mouse) twice a day for 2 days starting 2 weeks after γ-irradiation. One day after the final treatment, these mice were stimulated orally with 107 heat-killed E. faecalis. Two days after stimulation, F4/80+ MLN-Mϕ were isolated from these mice and tested for their M1Mϕ properties based on their abilities to express intracellular IL-12, CXCL9 and iNOS mRNA. In the results, Mϕ from WBI-mice treated with scrambled ODN did not express iNOS mRNA, intracellular IL-12 and CXCL9, even when these mice were stimulated with enterococcal antigen. However, iNOS+IL-12+CXCL9+ Mϕ were isolated from the same antigen-stimulated WBI-mice treated with CCL1 antisense ODN. These results indicate that M1Mϕ are inducible by the enterococcal antigen in WBI-mice treated with CCL1 antisense ODN.