Figure 2

Role of monocytes/macrophages in wound healing. Injury to epithelial and/or endothelial cells caused by various exogenous or endogenous factors resulting in tissue damage triggers complex interconnected wound-healing programs to restore tissue homeostasis. Release of DAMPs and PAMPS by the damaged tissue triggers an inflammatory response that activates resident tissue macrophages, stimulating their proliferation and initiating the recruitment of inflammatory Ly6C^hi monocytes and neutrophils to the wound. Cytokines and chemokines produced and secreted by local epithelial, endothelial and innate immune cells subsequently influence the differentiation and polarization of the recruited monocytes into inflammatory classically activated M1 macrophages. The M1 macrophages also stimulate the transdifferentiation of resident quiescent fibroblasts into activated myofibroblasts that synthesize a provisional matrix as well as stimulate endothelial cell and fibroblast proliferation and orchestrate angiogenesis. Recruited monocytes respond to the different cytokine profiles, differentiating into M2 macrophages and initiating tissue repair with upregulated MMP secretion followed by suppression of any remaining inflammation and synthesis of a permanent extracellular matrix by activated myofibroblasts. DAMPs, Damage associated molecular patterns; EC, Endothelial cell; ECM, Extracellular matrix; IFN, Interferon; iNOS, Inducible nitric oxide synthase; IL, Interleukin; MMP, Matrix metalloproteinase; PAMPs, Pathogen associated molecular patterns; TGF-β, Transforming growth factor, beta.