Phenotypic Transitions of Macrophages Orchestrate Tissue Repair

Abstract

Macrophages are essential for the efficient healing of numerous tissues, and they contribute to impaired healing and fibrosis. Tissue repair proceeds through overlapping phases of inflammation, proliferation, and remodeling, and macrophages are present throughout this progression. Macrophages exhibit transitions in phenotype and function as tissue repair progresses, although the precise factors regulating these transitions remain poorly defined. In efficiently healing injuries, macrophages present during a given stage of repair appear to orchestrate transition into the next phase and, in turn, can promote debridement of the injury site, cell proliferation and angiogenesis, collagen deposition, and matrix remodeling. However, dysregulated macrophage function can contribute to failure to heal or fibrosis in several pathological situations. This review will address current knowledge of the origins and functions of macrophages during the progression of tissue repair, with emphasis on skin and skeletal muscle. Dysregulation of macrophages in disease states and therapies targeting macrophage activation to promote tissue repair are also discussed.

Restoring Mucosal Barrier Function and Modifying Macrophage Phenotype with an Extracellular Matrix Hydrogel: Potential Therapy for Ulcerative Colitis

“…Recognition that effector cells of the immune system, such as the macrophages and Thelper cells, not only promote classic inflammatory processes but also orchestrate the temporal inhibition of inflammation and initiation of functional tissue remodeling [25,31,42,43,44,45] provides the opportunity to re-examine immunosuppressive strategies for treatment of diseases such as UC. Although the signaling molecules that influence macrophage and lymphocyte phenotype transition are not fully understood, there is suggestive evidence that at least some of these regulators reside within the ECM [9,10,25].…”

Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury

“…2 Macrophages undergo phenotypic and functional changes in each phase, and this ''functional plasticity'' leads to efficient wound healing and tissue repair after injury. 2 However, dysregulated macrophage activation can lead to impaired healing responses and chronic inflammation in several disease states.…”

“…2 Macrophages undergo phenotypic and functional changes in each phase, and this ''functional plasticity'' leads to efficient wound healing and tissue repair after injury. 2 However, dysregulated macrophage activation can lead to impaired healing responses and chronic inflammation in several disease states. 2 Microglia are the primary immune cells in the brain, and despite their distinct origin, 3 they share many phenotypic and functional properties with macrophages.…”

“…2 However, dysregulated macrophage activation can lead to impaired healing responses and chronic inflammation in several disease states. 2 Microglia are the primary immune cells in the brain, and despite their distinct origin, 3 they share many phenotypic and functional properties with macrophages. 4 For example, microglia respond to pro-inflammatory molecules, such as lipopolysaccharide (LPS) or interferon-c, to adopt a ''classical'' M1-like phenotype, which produces high levels of pro-inflammatory cytokines and oxidative metabolites that are essential for host defense and phagocytic activity.…”

In vivo association of immunophenotyped macrophages expressing CD163 with PDGF-B in gingival overgrowth-induced by three different categories of medications

“…12 Macrophages of M2c type express high levels of cluster of differentiation 163 (CD163), which has been shown to be associated with tissue repair and remodeling of the wound and promoting cell proliferation in mice. 13 In 2004, Lau et al 14 reported that CD163 immunoreactivity was observed in resident macrophages of all normal tissue samples including lymph node and tonsil, red pulp macrophages of spleen, bone marrow, alveolar macrophages of the lung, and Kupffer cells of the liver. CD163 is not expressed in splenic white pulp macrophages and germinal center tingible body macrophages.…”