Wound healing in MIP-1α−/− and MCP-1−/− mice

QEH Low, IA Drugea, LA Duffner, DG Quinn… - The American journal of …, 2001 - Elsevier
QEH Low, IA Drugea, LA Duffner, DG Quinn, DN Cook, BJ Rollins, EJ Kovacs, LA DiPietro
The American journal of pathology, 2001Elsevier
A salient feature of normal wound healing is the development and resolution of an acute
inflammatory response. Although much is known about the function of inflammatory cells
within wounds, little is known about the chemotactic and activation signals that influence this
response. As the CC chemokines macrophage inflammatory protein-1α (MIP-1α) and
monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was
examined in MIP-1α−/− and MCP-1−/− mice. Surprisingly, wound re-epithelialization …
A salient feature of normal wound healing is the development and resolution of an acute inflammatory response. Although much is known about the function of inflammatory cells within wounds, little is known about the chemotactic and activation signals that influence this response. As the CC chemokines macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was examined in MIP-1α−/− and MCP-1−/− mice. Surprisingly, wound re-epithelialization, angiogenesis, and collagen synthesis in MIP-1α−/− mice was nearly identical to wild-type controls. In contrast, MCP-1−/− mice displayed significantly delayed wound re-epithelialization, with the greatest delay at day 3 after injury (28 ± 5%versus 79 ± 14% re-epithelialization, P < 0.005). Wound angiogenesis was also delayed in MCP-1−/− mice, with a 48% reduction in capillary density at day 5 after injury. Collagen synthesis was impeded as well, with the wounds of MCP-1−/− mice containing significantly less hydroxyproline than those of control mice (25 ± 3 versus 50 ± 8 μg/wound at day 5, P < 0.0001). No change in the number of wound macrophages was observed in MCP-1−/− mice, suggesting that monocyte recruitment into wounds is independent of this chemokine. The data suggest that MCP-1 plays a critical role in healing wounds, most likely by influencing the effector state of macrophages and other cell types.
Elsevier