Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

By L. Arnold, A. Henry, F. Poron, Y. Baba-Amer, N. Van Rooijen, A. Plonquet, R. Gherardi, B. Chazaud. Journal of Experimental Medicine, 2007

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Macrophages (MPs) are important for skeletal muscle regeneration in vivo and may exert beneficial effects on myogenic cell growth through mitogenic and antiapoptotic activities in vitro. However, MPs are highly versatile and may exert various, and even opposite, functions depending on their activation state. We studied monocyte (MO)/MP phenotypes and functions during skeletal muscle repair. Selective labeling of circulating MOs by latex beads in CX3CR1GFP/+ mice showed that injured muscle recruited only CX3CR1lo/Ly-6C+ MOs from blood that exhibited a nondividing, F4/80lo, proinflammatory profile. Then, within muscle, these cells switched their phenotype to become proliferating antiinflammatory CX3CR1hi/Ly-6C− cells that further differentiated into F4/80hi MPs. In vitro, phagocytosis of muscle cell debris induced a switch of proinflammatory MPs toward an antiinflammatory phenotype releasing transforming growth factor β1. In co-cultures, inflammatory MPs stimulated myogenic cell proliferation, whereas antiinflammatory MPs exhibited differentiating activity, assessed by both myogenin expression and fusion into myotubes. Finally, depletion of circulating MOs in CD11b–diphtheria toxin receptor mice at the time of injury totally prevented muscle regeneration, whereas depletion of intramuscular F4/80hi MPs at later stages reduced the diameter of regenerating fibers. In conclusion, injured skeletal muscle recruits MOs exhibiting inflammatory profiles that operate phagocytosis and rapidly convert to antiinflammatory MPs that stimulate myogenesis and fiber growth.

Subfields: Biomedical Engineering, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c1b5feecbfeef3b8da88c0764e5bc8e8505731bc

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Citations in the corpus

Origin and Functions of Tissue Macrophages (2014, background): “Once in tissue, Ly6Chi monocytes can take on many characteristics of Ly6Clo monocytes (Arnold et al., 2007; Hilgendorf et al., 2014) and enter the lymphatics after such conversion (Qu et al., 2004) (Figure 2).”
Differential Roles of Macrophages in Diverse Phases of Skin Repair (2010, background): “Recent studies in mice report on a critical role of alternative macrophage activation for regeneration of skeletal muscle and myocardium postinjury (42, 43).”
Macrophage phenotypes during tissue repair (2013, background): “protein expression does not appear to correlate, negatively or otherwise, with protein expression of Ly6C [60], which is sometimes associated with a proinflammatory phenotype [24, 64, 75].”
Satellite Cells and Skeletal Muscle Regeneration (2015, positive): “Among the different factors present in the crushed muscle extract, TGF-β and HGF have been shown to directly increase the motility of myogenic cells.”
A Special Population of Regulatory T Cells Potentiates Muscle Repair (2013, neutral): “As anticipated (Arnold et al., 2007), there was a rapid increase in CD11b+Gr1 myeloid mononuclear cells beginning before day 1, initially a proinflammatory Ly6chi population but switching to an anti-inflammatory Ly6clo population by day 4 (Figure 1A, top).”
Blood monocytes: development, heterogeneity, and relationship with dendritic cells. (2009, background): “(151) concluded that Ly6C+ (Gr1+) monocytes had differentiated into Ly6C− (Gr1−) monocytes, whereas the studies by Auffray et al.”
Microglial M1/M2 polarization and metabolic states (2016, background): “…distinct subpopulations that, within different stages of an inflammatory response, would perform different functions (Auffray et al., 2007; Nahrendorf et al., 2007) or rather, shift between functional phenotypes depending upon environmental signals (Arnold et al., 2007; Crane et al., 2014).”
Macrophages are required for neonatal heart regeneration. (2014, positive): “In skeletal muscle, regeneration following toxic injury depends on monocyte/macrophage stimulation of myogenic proliferation (33) and remyelination in the aging central nervous system is stimulated by recruitment of young monocytes (32).”
A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth (2009, background): “They are however, similar to a recently identified anti-inflammatory macrophage important in facilitating myogenesis in terms of Gr1 expression [65].”
Role of Human Macrophage Polarization in Inflammation during Infectious Diseases (2018, background): “However, such responses must be controlled to prevent tissue damage to the host and avoid severe immunopathologies through the production by M2-polarized macrophages of anti-inflammatory cytokine mediators, cytokines, and chemokines that will regulate M1 macrophages, extenuate inflammatory reactions”
Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype (2016, background): “In skeletal muscle injury, the macrophages involved in muscle regeneration have been characterized as M2c macrophages that exhibit anti-inflammatory properties by releasing TGF-b and by neutralizing pro-inflammatory M1 macrophages.(35) In post-MI repair, M2c marker MertK-expressing macrophages play ”