Abstract
Macrophages and inflammation play a beneficial role during wound repair with macrophages regulating a wide range of processes, such as removal of dead cells, debris and pathogens, through to extracellular matrix deposition re-vascularisation and wound re-epithelialisation. To perform this range of functions, these cells develop distinct phenotypes over the course of wound healing. They can present with a pro-inflammatory M1 phenotype, more often found in the early stages of repair, through to anti-inflammatory M2 phenotypes that are pro-repair in the latter stages of wound healing. There is a continuum of phenotypes between these ranges with some cells sharing phenotypes of both M1 and M2 macrophages. One of the less pleasant consequences of quick closure, namely the replacement with scar tissue, is also regulated by macrophages, through their promotion of fibroblast proliferation, myofibroblast differentiation and collagen deposition. Alterations in macrophage number and phenotype disrupt this process and can dictate the level of scar formation. It is also clear that dysregulated inflammation and altered macrophage phenotypes are responsible for hindering closure of chronic wounds. The review will discuss our current knowledge of macrophage phenotype on the repair process and how alterations in the phenotypes might alter wound closure and the final repair quality.
Highlights
To overcome the repeated dermal insults and injuries that occur on a daily basis, evolution has provided a swift but robust mechanism for tissue repair
Pro-inflammatory mediators interferon-γ (IFN-γ) and tumour necrosis factor (TNF), and damage associated pattern molecules (DAMPs) activate cells to produce ‘classically activated’ M1 macrophages (Figure 1) [11]. This results in a pro-inflammatory macrophage phenotype that prolifically produces pro-inflammatory cytokines, such as TNF and Interleukin-6 (IL-6), and other mediators that facilitate the initial stages of wound healing (Figure 1)
This suggests that the small population of resident macrophages might play different roles to the recruited macrophages derived from monocytes during the wound repair process, but this has yet to be tested
Summary
To overcome the repeated dermal insults and injuries that occur on a daily basis, evolution has provided a swift but robust mechanism for tissue repair. At the start of the repair process, blood loss is stemmed by formation of a blood clot containing platelets, red blood cells, white blood cells and fibrin fibers These fibers act as a scaffold for immune cells that are attracted by soluble factors released from platelets and injured tissue, to enter the wound. Wound associated macrophage numbers increase until day 2 when their numbers remain stable until around day 5 when they begin to gradually decrease to steady state levels by day 14 [5] During this time in the wound, macrophages remove spent neutrophils and secrete various cytokines, growth factors and other mediators [6]. Macrophages can release enzymes that alter the composition of the ECM and the structure of the wound
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