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

Am J Pathol. 2001 Aug;159(2):457-63. doi: 10.1016/s0002-9440(10)61717-8.


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-1alpha (MIP-1alpha) and monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was examined in MIP-1alpha(-/-) and MCP-1(-/-) mice. Surprisingly, wound re-epithelialization, angiogenesis, and collagen synthesis in MIP-1alpha(-/-) 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 microg/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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokine CCL2 / deficiency
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / physiology*
  • Chemokine CCL3
  • Chemokine CCL4
  • Collagen / biosynthesis
  • Epithelial Cells / pathology
  • Epithelial Cells / physiology
  • Macrophage Inflammatory Proteins / deficiency
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / physiology*
  • Macrophages / pathology
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Physiologic
  • Skin / pathology
  • Time Factors
  • Wound Healing / genetics
  • Wound Healing / physiology*
  • Wounds and Injuries / pathology


  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Macrophage Inflammatory Proteins
  • Collagen