MIP-1α as a critical macrophage chemoattractant in murine wound repair

At sites of injury, macrophages secrete growth factors and proteins that promote tissue repair. While this central role of the macrophage has been well studied, the specific stimuli that recruit macrophages into sites of injury are not well understood. This study examines the role of macrophage inflammatory protein 1 alpha (MIP-1 alpha), a C-C chemokine with monocyte chemoattractant capability, in excisional wound repair. Both MIP-1 alpha mRNA and protein were detectable in murine wounds from 12 h through 5 d after injury. MIP-1 alpha protein levels peaked 3 d after injury, coinciding with maximum macrophage infiltration. The contribution of MIP-1 alpha to monocyte recruitment into wounds was assessed by treating mice with neutralizing anti-MIP-1 alpha antiserum before injury. Wounds of mice treated with anti-MIP-1 alpha antiserum had significantly fewer macrophages than control (41% decrease, P < 0.01), This decrease in wound macrophages was paralleled by decreased angiogenic activity and collagen synthesis. When tested in the corneal micropocket assay, wound homogenates from mice treated with anti-MIP-1 alpha contained significantly less angiogenic activity than control wound homogenates (27% positive for angiogenic activity versus 91% positive in the control group, P < 0.01). Collagen production was also significantly reduced in the wounds from anti-MIP-1 alpha treated animals (29% decrease, P < 0.05). The results demonstrate that MIP-1 alpha plays a critical role in macrophage recruitment into wounds, and suggest that appropriate tissue repair is dependent upon this recruitment.