Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 175, Issue 6, Pages 2454-2462Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.090248
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Funding
- NIGMS NIH HHS [R01 GM050875, P20 GM078426, P20-GM078426, R01-GM50875] Funding Source: Medline
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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-a and reduced levels of transforming growth factor-beta 1 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. (Am J Pathol 2009, 175:2454-2462; DOI: 10.2353/ajpath.2009.090248)
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