Cited by 2,002Muscle Physiology and DisordersWound Healing and TreatmentsImmune cells in cancer

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

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Arnold, Ludovic, Henry, Adeline, Poron, Françoise, Baba-Amer, Yasmine, van Rooijen, Nico, Plonquet, Anne, Gherardi, Romain K., Chazaud, Bénédicte·2007·The Journal of Experimental Medicine

DOI 10.1084/jem.20070075PMC PMC2118577

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Abstract

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.

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Authors: Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B.
Affiliations: Inserm (FR)
Université Paris-Est Créteil (FR)
1Institut National de la Santé et de la Recherche Médicale, Unité 841, Institut Mondor de Recherche Biomédicale, “Cell Interactions in the Neuromuscular System” Team, Université Paris 12 Val-de-Marne, 94000 Créteil, France
Vrije Universiteit Amsterdam (NL)
Assistance Publique – Hôpitaux de Paris (FR)
ORCID: van Rooijen, Nico
Gherardi, Romain K.
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2007-05-07
Volume: 204
Issue: 5
Pages: 1057-1069
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20070075
PMC: PMC2118577
OpenAlex: W2108723188
Cited by: 2,002
References: 82
Citations by year: 2026: 87 · 2025: 83 · 2024: 100 · 2023: 119 · 2022: 124 · 2021: 151 · 2020: 144 · 2019: 134 · 2018: 131 · 2017: 147 · 2016: 119 · 2015: 127 · 2014: 120 · 2013: 101 · 2012: 89
FWCI: 20.15
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: cc-by-nc-sa
Locations: The Journal of Experimental Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Funders: Institut National de la Santé et de la Recherche Médicale
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Surgery › Wound Healing and Treatments
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: inflammatory monocytes, macrophage polarization, skeletal muscle regeneration, myogenesis, CX3CR1, Ly6C, F4/80, TGF-β1, myotube formation, monocyte depletion, muscle damage
MeSH terms: CX3C Chemokine Receptor 1, Animals, Cell Differentiation, Humans, Immunohistochemistry, Macrophages, Mice, Mutant Strains, Microspheres, Monocytes, Phagocytosis, DNA Primers, Muscle, Skeletal, Receptors, Chemokine, Reverse Transcriptase Polymerase Chain Reaction, Muscle Development, CD11b Antigen, Green Fluorescent Proteins, Mice

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

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