Wound macrophages exhibit a complex phenotype, which changes as the wound matures and develops independently of IL-4 or IL-13.

The phenotype of wound macrophages has not been studied by direct examination of these cells, yet macrophages recruited to sites of injury are described as alternatively activated macrophages, requiring IL-4 or IL-13 for phenotypic expression. This study characterized wound macrophage phenotype in the PVA sponge wound model in mice. Eighty-five percent of wound macrophages isolated 1 day after injury expressed Gr-1, but only 20% of those isolated at 7 days expressed this antigen. Macrophages from 1-, 3-, and 7-day wounds expressed markers of alternative activation, including mannose receptor, dectin-1, arginase 1, and Ym1, but did not contain iNOS. Day 1 wound macrophages produced more TNF-α, more IL-6, and less TGF-β than Day 7 wound macrophages. Wound macrophages did not produce IL-10. The cytokines considered necessary for alternative activation of macrophages, IL-4 and IL-13, were not detected in the wound environment and were not produced by wound cells. Wound macrophages did not contain PStat6. Wound fluids inhibited IL-13-dependent phosphorylation of Stat6 and contained IL-13Rα2, a soluble decoy receptor for IL-13. The phenotype of wound macrophages was not altered in mice lacking IL-4Rα, which is required for Stat6-dependent signaling of IL-4 and IL-13. Wound macrophages exhibit a complex phenotype, which includes traits associated with alternative and classical activation and changes as the wound matures. The wound macrophage phenotype does not require IL-4 or IL-13.