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Updated: Jun 19, 2026
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
Selective and specific macrophage ablation is detrimental to wound healing in mice
Rita Mirza1, Luisa A DiPietro, Timothy J Koh
1Department of Kinesiology and Nutrition, Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Abstract:
Macrophages are thought to play important roles during wound healing, but definition of these roles has been hampered by our technical inability to specifically eliminate macrophages during wound repair. The purpose of this study was to test the hypothesis that specific depletion of macrophages after excisional skin wounding would detrimentally affect healing by reducing the production of growth factors important in the repair process. We used transgenic mice that express the human diphtheria toxin (DT) receptor under the control of the CD11b promoter (DTR mice) to specifically ablate macrophages during wound healing. Mice without the transgene are relatively insensitive to DT, and administration of DT to wild-type mice does not alter macrophage or other inflammatory cell accumulation after injury and does not influence wound healing. In contrast, treatment of DTR mice with DT prevented macrophage accumulation in healing wounds but did not affect the accumulation of neutrophils or monocytes. Such macrophage depletion resulted in delayed re-epithelialization, reduced collagen deposition, impaired angiogenesis, and decreased cell proliferation in the healing wounds. These adverse changes were associated with increased levels of tumor necrosis factor-alpha and reduced levels of transforming growth factor-beta1 and vascular endothelial growth factor in the wound. In summary, macrophages seem to promote both wound closure and dermal healing, in part by regulating the cytokine environment of the healing wound.
Insights
Macrophages are crucial for effective wound healing. Depleting these cells delays skin repair, reduces collagen, and impairs blood vessel formation, highlighting their essential role in the healing process.
Area of Science:
- Immunology
- Regenerative Medicine
- Dermatology
Background:
- Macrophages are implicated in wound healing, but their specific roles are unclear due to difficulties in their targeted elimination.
- Understanding macrophage functions is vital for developing therapies to improve wound repair outcomes.
Purpose of the Study:
- To investigate the impact of specific macrophage depletion on excisional skin wound healing.
- To test if eliminating macrophages impairs growth factor production and delays the repair process.
Main Methods:
- Utilized transgenic mice (DTR mice) expressing the diphtheria toxin receptor under the CD11b promoter for targeted macrophage ablation.
- Administered diphtheria toxin (DT) to DTR mice to deplete macrophages at the wound site.
- Assessed wound healing parameters including re-epithelialization, collagen deposition, angiogenesis, and cell proliferation.
Main Results:
- Macrophage depletion in DTR mice significantly delayed re-epithelialization, reduced collagen deposition, impaired angiogenesis, and decreased cell proliferation.
- Macrophage ablation led to increased tumor necrosis factor-alpha and decreased transforming growth factor-beta1 and vascular endothelial growth factor levels in wounds.
- Neutrophil and monocyte accumulation remained unaffected by DT treatment in DTR mice.
Conclusions:
- Macrophages play a critical role in promoting both wound closure and dermal healing.
- Macrophage functions in wound repair are partly mediated by regulating the local cytokine environment.
- Targeting macrophages could be a therapeutic strategy to enhance wound healing.
