Heterogeneity of Macrophage Populations and Expression of Galectin-3 in Cutaneous Wound Healing in Rats

The aim of this study was to investigate the properties of macrophages that infiltrated the sites of cutaneous wound healing in rats between 1 and 26 days post wounding (dpw). During the inflammation phase (1–3 dpw), ED1 + (CD68 +) macrophages with enhanced lysosomal activity dominated. From 5 to 7 dpw there was formation of granulation tissue as indicated by the presence of myofibroblasts expressing α-smooth muscle actin. At this stage, ED2 + (CD163 +) macrophages, capable of producing inflammatory factors, were dominant. The majority of ED1 + macrophages expressed galectin-3, a regulator of fibrosis. Corresponding to the increased numbers of ED1 + and ED2 + macrophages at 3–9 dpw, there was increased expression of genes encoding transforming growth factor-β1 (a major fibrogenic factor), monocyte chemoattractant protein-1 and colony stimulating factor-1. These macrophage-related factors might contribute to inflammation and formation of granulation tissue. OX6 + macrophages expressing class II molecules of the major histocompatibility complex became predominant in the healing stages (15–26 dpw), indicating important roles for antigen-presenting cells in tissue remodelling. The OX6 + macrophages were most likely derived from ED1 + macrophages. The results of this study show that infiltration of phenotypically- and functionally-distinct macrophage populations characterizes different stages of the wound healing process.