038 Adenoviral overexpression of MCP‐2 induces macrophages and improves wound healing in diabetic rats

The recruitment of leukocyte subsets is mainly driven by chemokines. Monocyte chemotactic protein-2 (MCP-2) belongs to the CC subfamily of chemokines, and it is especially a chemoattractant for monocytes. Of all CC subfamily members only MCP-2 interacts with multiple receptors, and its N-terminal truncated isoform is a natural chemokine inhibitor. Gene expression profiling in excisional wounds showed MCP-2 was down-regulated 40% in wild type mice and 69.2% in diabetic mice at 24 h after wounding. To determine the biological response to MCP-2 during wound healing, we constructed an adenoviral vector (Ad-MCP-2). Ad-MCP-2 infected cell conditioned medium contained 460 ng/ml secreted MCP-2 (ELISA) and had chemotactic activity similar to recombinant full-length MCP-2 but not to MCP-2 N-terminal 8–13aa peptides in a THP-1cell migration assay. In an incisional wound model in STZ induced diabetic rats, the breaking strength of Ad-MCP-2 infected skin wounds increased by 43%(108 PFU, p < 0.05) and 30%(107 PFU, p < 0.05) at 7d after Ad-MCP-2 injection compared with Ad-LacZ control. The wound closure strength of 107 PFU Ad-MCP-2 infected wounds still increased by 21%(p < 0.05) at 10d after injection. In normal rats, the breaking strength of Ad-MCP-2 and Ad-Lacz infected wounds was not significantly different. In rats, we injected either Ad-MCP-2 or Ad-LacZ (108 PFU) into each PVA sponge at 3d after implantation. Histological analyses revealed numerous ED-1 positive macrophages infiltrating in the experimental granulation tissue at 7d after Ad-MCP-2 injection. Our data provide evidence that MCP-2 improved wound healing in diabetic rats, and the recruitment of macrophages into the wound granulation tissues was the one of the mechanisms.