Macrophage phenotypes during tissue repair

Mp are crucial for tissue repair and regeneration but can also contribute to tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory "M1" phenotype, produced by exposure to IFN-γ and TNF-α, and an anti-inflammatory "M2a" phenotype, produced by IL-4 or IL-13. M2a Mp are frequently termed "wound healing" Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro-defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1- and M2-associated markers may be expressed simultaneously by actual tissue-repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.