Macrophages Protect against Muscle Atrophy and Promote Muscle Recovery in Vivo and in Vitro

Dumont, Nicolas A.; Frenette, Jérôme

doi:10.2353/ajpath.2010.090884

Cited by 87 publications

(42 citation statements)

References 59 publications

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“…In particular, the finding that anti-inflammatory macrophages express IGF-1 and are protective of muscle size during atrophy is of interest in our study (Dumont and Frenette, 2010). Muscle reloading after atrophy has been shown to be associated with early damage and a transient inflammatory response (Oishi et al, 2008; St Pierre and Tidball, 1994; Tidball and Wehling-Henricks, 2007) and this inflammatory response seems critical for full recovery as a decrease in macrophages or IL-6 inhibits regrowth (Tidball and Wehling-Henricks, 2007; Washington et al, 2011).…”

Section: Discussionmentioning

confidence: 87%

Regrowth after skeletal muscle atrophy is impaired in aged rats, despite similar responses in signaling pathways

White

Confides

Moore

et al. 2015

Experimental Gerontology

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Skeletal muscle regrowth after atrophy is impaired in the aged and in this study we hypothesized that this can be explained by a blunted response of signaling pathways and cellular processes during reloading after hind limb suspension in muscles from old rats. Male Brown Norway Fisher 344 rats at 6 (young) and 32 (old) months of age were subjected to normal ambulatory conditions (amb), hind limb suspension for 14 days (HS), and HS followed by reloading through normal ambulation for 14 days (RE); soleus muscles were used for analysis of intracellular signaling pathways and cellular processes. Soleus muscle regrowth was blunted in old compared to young rats which coincided with a recovery of serum IGF-1 and IGFBP-3 levels in young but not old. However, the response to reloading for p-Akt, p-p70s6k and p-GSK3β protein abundance was similar between muscles from young and old rats, even though main effects for age indicate an increase in activation of this protein synthesis pathway in the aged. Similarly, MAFbx mRNA levels in soleus muscle from old rats recovered to the same extent as in the young, while Murf-1 was unchanged. mRNA abundance of autophagy markers Atg5 and Atg7 showed an identical response in muscle from old compared to young rats, but beclin did not. Autophagic flux was not changed at either age at the measured time point. Apoptosis was elevated in soleus muscle from old rats particularly with HS, but recovered in HSRE and these changes were not associated with differences in caspase-3, -8 or-9 activity in any group. Protein abundance of apoptosis repressor with caspase-recruitment domain (ARC), cytosolic EndoG, as well as cytosolic and nuclear apoptosis inducing factor (AIF) were lower in muscle from old rats, and there was no age-related difference in the response to atrophy or regrowth. Soleus muscles from old rats had a higher number of ED2 positive macrophages in all groups and these decreased with HS, but recovered in HSRE in the old, while no changes were observed in the young. Pro-inflammatory cytokines in serum did not show a differential response with age to different loading conditions. Results indicate that at the measured time point the impaired skeletal muscle regrowth after atrophy in aged animals is not associated with a general lack of responsiveness to changes in loading conditions.

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Section: Discussionmentioning

confidence: 87%

Regrowth after skeletal muscle atrophy is impaired in aged rats, despite similar responses in signaling pathways

White

Confides

Moore

et al. 2015

Experimental Gerontology

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“…After toxin-induced injury to skeletal muscle, CD206 + MΦ and Ly6C lo MO accumulate during the secondary phase of healing and are required for complete regeneration, likely because they stimulate myotube fusion[19]. COX-2 lo MΦ, which are phenotypically similar to CD206 + MΦ, protect myotubes against atrophy in vitro [47]. In contrast, classical Ly6C hi MO promote chronic muscle degeneration in mdx mice[48].…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Immune Cell Subset Infiltration of Supraspinatus Muscle After Severe Rotator Cuff Injury

Krieger

Tellier

Ollukaren

et al. 2017

Regen. Eng. Transl. Med.

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Rotator cuff tears cause muscle degeneration that is characterized by myofiber atrophy, fatty infiltration, and fibrosis and is minimally responsive to current treatment options. The underlying pathogenesis of rotator cuff muscle degeneration remains to be elucidated, and increasing evidence implicates immune cell infiltration as a significant factor. Because immune cells are comprised of highly heterogeneous subpopulations that exert divergent effects on injured tissue, understanding trafficking and accumulation of immune subpopulations may hold the key to more effective therapies. The present study quantifies subpopulations of immune cells infiltrating the murine supraspinatus muscle after severe rotator cuff injury that includes tenotomy and denervation. Rotator cuff injury stimulates dramatic infiltration of mononuclear phagocytes, enriches mononuclear phagocytes in non-classical subpopulations, and enriches T lymphocytes in TH and Treg subpopulations. The combination of tenotomy plus denervation significantly increases mononuclear phagocyte infiltration, enriches macrophages in the non-classical subpopulation, and decreases T lymphocyte enrichment in TH cells compared to tenotomy alone. Depletion of circulating monocytes via liposomal clodronate accelerates supraspinatus atrophy after tenotomy and denervation. The study may aid rational design of immunologically smart therapies that harness immune cells to enhance outcomes after rotator cuff tears.

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“…Skeletal muscles are known for complex muscle biology, and recent studies have shown that MØs play a significant role in helping muscle regeneration and preventing muscle atrophy (9, 48–50) via cell-to-cell contacts (14). The role of stem and hematopoietic cells in muscle regeneration has been also extensively studied (51, 52).…”

Section: Discussionmentioning

confidence: 99%

Horizontal gene transfer from macrophages to ischemic muscles upon delivery of naked DNA with Pluronic block copolymers

et al. 2016

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Intramuscular administration of plasmid DNA (pDNA) with non-ionic Pluronic block copolymers increases gene expression in injected muscles and lymphoid organs. We studied the role of immune cells in muscle transfection upon inflammation. Local inflammation in murine hind limb ischemia model (MHLIM) drastically increased DNA, RNA and expressed protein levels in ischemic muscles injected with pDNA/Pluronic. The systemic inflammation (MHLIM or peritonitis) also increased expression of pDNA/Pluronic in the muscles. When pDNA/Pluronic was injected in ischemic muscles the reporter gene, Green Fluorescent Protein (GFP) co-localized with desmin+ muscle fibers and CD11b+ macrophages (MØs), suggesting transfection of MØs along with the muscle cells. P85 enhanced (~4 orders) transfection of MØs with pDNA in vitro. Moreover, adoptively transferred MØs were shown to pass the transgene to inflamed muscle cells in MHLIM. Using a co-culture of myotubes (MTs) and transfected MØs expressing a reporter gene under constitutive (cmv-luciferase) or muscle specific (desmin-luciferase) promoter we demonstrated that P85 enhances horizontal gene transfer from MØ to MTs. Therefore, MØs can play an important role in muscle transfection with pDNA/Pluronic during inflammation, with both inflammation and Pluronic contributing to the increased gene expression. pDNA/Pluronic has potential for therapeutic gene delivery in muscle pathologies that involve inflammation.

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Macrophages Protect against Muscle Atrophy and Promote Muscle Recovery in Vivo and in Vitro

Cited by 87 publications

References 59 publications

Regrowth after skeletal muscle atrophy is impaired in aged rats, despite similar responses in signaling pathways

Regrowth after skeletal muscle atrophy is impaired in aged rats, despite similar responses in signaling pathways

Quantitative Analysis of Immune Cell Subset Infiltration of Supraspinatus Muscle After Severe Rotator Cuff Injury

Horizontal gene transfer from macrophages to ischemic muscles upon delivery of naked DNA with Pluronic block copolymers

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