Selective and Specific Macrophage Ablation Is Detrimental to Wound Healing in Mice
Open accessAbstract
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 envi…
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Depletion of macrophages during the proliferative phase of wound healing results in a defective transition to the remodeling phase and impaired healing.
“A recent study showed that depletion of macrophages during the proliferative phase of wound healing resulted in a defective transition to the remodeling phase and impaired healing [106,107].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [107]
Accumulating evidence indicates that macrophages are critical orchestrators in healing of many tissues, including skin.
“Accumulating evidence indicates that Mp are critical orchestrators in healing of many tissues, including skin (3,4,7,48).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [4]
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- Authors
- Mirza, R., DiPietro, L. A., & Koh, T. J.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Koh, Timothy J.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 175
- Issue
- 6
- Pages
- 2454-2462
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2789630
- OpenAlex
- W1977631233
- Cited by
- 616
- References
- 6
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 42 · 2023: 29 · 2022: 48 · 2021: 41 · 2020: 41 · 2019: 43 · 2018: 36 · 2017: 47 · 2016: 48 · 2015: 35 · 2014: 47 · 2013: 43 · 2012: 27
- FWCI
- 23.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p20gm078426-04, GM-50875)
- National Institute of General Medical Sciences (R01GM050875, P20‐GM078426)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- macrophages, wound healing, macrophage depletion, diphtheria toxin receptor, CD11b, excision wound, re-epithelialization, collagen deposition, angiogenesis, TNF-α, TGF-β1, vascular endothelial growth factor, cytokine environment
- MeSH terms
- Animals, Diphtheria Toxin, Humans, Image Processing, Computer-Assisted, Macrophages, Mice, Transgenic, Skin, Wound Healing, Neovascularization, Physiologic, Intercellular Signaling Peptides and Proteins, Mice
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