Wound healing in MIP-1 alpha(-/-) and MCP-1(-/-) mice

A salient feature of normal wound healing is the development and resolution of an acute inflammatory response. Although much is known about the functi on of inflammatory cells within wounds, little is known about the chemotact ic and activation signals that influence this response. As the CC chemokine s macrophage inflammatory protein-1 alpha (MEP-1 alpha) and monocyte chemot actic protein-1 (MCP-1) are abundant in acute wounds, wound repair was exam ined in MIP-1 alpha (-/-) and MCP-1(-/-) mice. Surprisingly, wound re-epith elialization, angiogenesis, and collagen synthesis in MIP-1 alpha (-/-) mic e was nearly identical to wildtype controls. In contrast, MCP-1(-/-) mice d isplayed significantly delayed wound re-epithelialization, with the greates t delay at day 3 after injury (28 +/- 5% versus 79 +/- 14% re-epithelializa tion, P < 0.005). Wound angiogenesis was also delayed in MCP-1(-/-) mice, w ith a 48% reduction in capillary density at day 5 after injury. Collagen sy nthesis was impeded as well, with the wounds of MCP-1(-/-) mice containing significantly less hydroxyproline than those of control mice (25 <plus/minu s> 3 versus 50 +/- 8 mug/wound at day 5, P < 0.0001). No change in the numb er of wound macrophages was observed in MCP-1(-/-) mice, suggesting that mo nocyte recruitment into wounds is independent of this chemokine. The data s uggest that MCP-1 plays a critical role in healing wounds, most likely by i nfluencing the effector state of macrophages and other cell types.