Influence of M2b macrophage elimination on the wound healing responses in severely burned mice

Abstract

Abstract To restore the impaired antibacterial resistance of burn patients, we performed M2bMϕ elimination using CCL1 antisense ODN. However, our treatment with the M2bMϕ polarizer includes a concern about the delay or disturbance of wound healing, because M2a and M2cMϕ distributed in tissues surrounding the burn area are known to be indispensable for host wound healing responses. In this study, the influence of M2bMϕ elimination on wound healing responses was investigated in severely burned mice. Mice 10 days after burn injury (day-10 burn mice) were treated with the ODN (s.c., 10 μg/mouse). Dermal F4/80+ cells (Mϕ) from these mice were analyzed for the expression of IL-10 (a biomarker of M2Mϕ), Arg1 and Ym1 (biomarkers of M2a and M2cMϕ), and LIGHT (a biomarker of M2bMϕ). Also, these dermal Mϕ were tested for the production of fibronectin and collagen (wound healing-related soluble factors) by ELISA. In the results, the increased expression of IL-10, Arg1, Ym1, and LIGHT mRNA was shown in dermal F4/80+ cells of day-10 burn mice, as compared to that of normal mice. Similarly, Arg1 and Ym1 mRNAs, but not LIGHT mRNA, were expressed by the same cells of day-10 burned mice treated with the ODN. Similar amounts of wound healing-related soluble factors were produced by dermal Mϕ from day-10 burned mice and the same mice treated with the ODN. These results indicate that the delay or disturbance of wound healing is minimal in severely burned hosts with eliminated M2bMϕ.