Modulation of JE/MCP-1 expression in dermal wound repair

The tissue macrophage plays a prominent role in wound repair, yet the parameters that influence macrophage migration into the wound bed are not well understood. To better understand the process of macrophage recruitment, the production of JE, the murine homologue of monocyte chemoattractant protein 1(JE/MCP-1), was examined in a murine model of dermal wound repair. High levels of JE/MCP-1 mRNA were found in dermal punch wounds at 12 hours and 1 day (24 hours) after wounding; mRNA levels slowly decreased to undetectable by day 21. In situ hybridization analysis of wounds revealed that JE/MCP-1 was predominantly expressed by monocytic and macrophage-like cells, as well as by occasional fibroblasts and other interstitial cells. To correlate JE/MCP-1 production with macrophage migration, macrophage infiltration into the wound bed was quantitated. The number of macrophages within the wound increased to a maximum at day 3 (11.3 +/- 4.5 macrophages per high power field), began to decrease at day 5 (4.8 +/- 1.9 macrophages per high power field), and reached near base line at day 10 (3.0 +/- 1.1 macrophages per high power field). The results demonstrate that JE/MCP-1 production within wounds is closely linked to the time course and distribution of macrophage infiltration, with maximal JE/MCP-1 mRNA levels occurring 1 to 2 days before maximal macrophage infiltration. The results support a role for JE/MCP-1 in the recruitment of wound macrophages and suggest that macrophages, through the production of JE/MCP-1, may sustain the recruitment of additional monocytes and macrophages into sites of injury.