Macrophage polarity and wound age determination

Abstract

Abstract We investigated the dynamics of the gene expression of M1 and M2 macrophage markers during skin wound healing in mice. Expression of M1-macrophage markers, such as Il12a, Tnf, Il6, Il1b, and Nos2 was upregulated after wounding and peaked at 1 or 3 days after injury, and that of M2-macrophage markers such as Mrc1, Cd163, Ccl17, Arg, and Tgfb1, peaked at 6 days after injury. Consistent with these findings, using double-color immunofluorescence analysis revealed that CD80-positive M1 macrophages were more abundant than CD206-positive M2 macrophages on day 3 in mouse wound specimens, and that M2 macrophages were prominently detected in day 6 wounds. For application in forensic practice, we examined macrophage polarization using human wound specimens. The average ratios of HLA-DRα-positive M1 macrophages to CD163-positive M2 macrophages (M1/M2 ratios) were greater than 2.0 for the wounds aged 2–5 days. Furthermore, six of the eight samples individually exceeded the M1/M2 ratio of 2.0 in the range of 1.88–4.30. Therefore, an M1/M2 ratio significantly above 2.0 strongly indicates a wound age of 2–5 days. This study showed that M1 and M2 macrophages in human skin wound might be a promising marker for wound age determination.