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

SummaryThe 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.