Macrophages in Injured Skeletal Muscle: A Perpetuum Mobile Causing and Limiting Fibrosis, Prompting or Restricting Resolution and Regeneration

Bosurgi, Lidia; Manfredi, Angelo A.; Rovere‐Querini, Patrizia

doi:10.3389/fimmu.2011.00062

Cited by 67 publications

(66 citation statements)

References 162 publications

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“…Exercise increases muscle mass, in part, through activation of macrophages. 34,35 The type of macrophage involved in the macrophage response depends on their function. M1 killer macrophages are involved in phagocytosis or meeting a microbe challenge, which leads to a sustained inflammation.…”

Section: Discussionmentioning

confidence: 99%

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Klein

Hassounah

et al. 2015

Journal of the American Society of Nephrology

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Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Lowfrequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-g and IL-6) increased. Expression of the M1 macrophage marker IL-1b also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKDinduced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.

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Section: Discussionmentioning

confidence: 99%

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Klein

Hassounah

et al. 2015

Journal of the American Society of Nephrology

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“…Muscle stem cells fail to activate their regenerative potential in the absence of the inflammatory response. 66,70,74 The release of DAMPs/alarmins as a consequence of cell death and of immune cell activation might be important in the reciprocal activation/regulation of immune and of muscle stem/progenitor cells. The availability of novel elegant genetic inducible cell-fate mapping models will be valuable for the better understanding of the overall scenario.…”

Section: The Regeneration Of Injured Muscles Depends On Inflammationmentioning

confidence: 99%

“…Their depletion results in the persistence of cell remnants, deriving either from necrotic fibers, dying progenitor cells or inflammatory leukocytes. Moreover, upon depletion of macrophages muscle regeneration is severely compromised (reviewed in Bosurgi et al 70 and Tidballand and Villalta 71 ). Macrophages and muscle regeneration are therefore closely associated.…”

Section: The Predators: Macrophages Scavenge Muscle Debrismentioning

confidence: 99%

Cell death, clearance and immunity in the skeletal muscle

et al. 2016

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“…Keeling et al (25) further reported that M-CSF-induced macrophage differentiation stimulated the increase of nuclear number and myotube elongation in C2C12 cells. These results clearly indicate the beneficial effects of macrophages during the response to muscle injury, although detrimental actions of macrophages are also reported (5,56,57), suggesting the divergent roles of macrophages.…”

Section: Responses To Reloadingmentioning

confidence: 73%

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers

Ohira

Wang

Ito

et al. 2015

American Journal of Physiology-Cell Physiology

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Effects of macrophage on the responses of soleus fiber size to hind limb unloading and reloading were studied in osteopetrotic homozygous (op/op) mice with inactivated mutation of macrophage colony-stimulating factor (M-CSF) gene and in wild-type (ϩ/ϩ) and heterozygous (ϩ/op) mice. The basal levels of mitotically active and quiescent satellite cell (Ϫ46 and Ϫ39% vs. ϩ/ϩ, and Ϫ40 and Ϫ30% vs. ϩ/op) and myonuclear number (Ϫ29% vs. ϩ/ϩ and Ϫ28% vs. ϩ/op) in fibers of op/op mice were significantly less than controls. Fiber length and sarcomere number in op/op were also less than ϩ/ϩ (Ϫ22%) and ϩ/op (Ϫ21%) mice. Similar trend was noted in fiber cross-sectional area (CSA, Ϫ15% vs. ϩ/ϩ, P ϭ 0.06, and Ϫ14% vs. ϩ/op, P ϭ 0.07). The sizes of myonuclear domain, cytoplasmic volume per myonucleus, were identical in all types of mice. The CSA, length, and the whole number of sarcomeres, myonuclei, and mitotically active and quiescent satellite cells, as well as myonuclear domain, in single muscle fibers were decreased after 10 days of unloading in all types of mice, although all of these parameters in ϩ/ϩ and ϩ/op mice were increased toward the control values after 10 days of reloading. However, none of these levels in op/op mice were recovered. Data suggest that M-CSF and/or macrophages are important to activate satellite cells, which cause increase of myonuclear number during fiber hypertrophy. However, it is unclear why their responses to general growth and reloading after unloading are different. myonuclei; muscle fiber size; osteopetrotic mice; satellite cells; unloading and reloading SKELETAL MUSCLES ARE COMPOSED of multinucleated muscle fibers and have an extensive capacity for morphological and functional adaptation. For example, chronic unloading of muscles by bedrest in humans (45,46,64) and hind limb suspension and actual spaceflight in animals (6, 40 -42, 47, 59) result in muscle fiber atrophy and a shift toward a faster myosin heavy chain profile, particularly in antigravity muscles composed predominantly of slow-twitch fibers, such as the soleus (6,42,(45)(46)(47) and adductor longus (41, 59). Muscle fiber atrophy and the shift toward a faster myosin heavy chain profile are reversed in response to muscle reloading (41,45,46,59). The muscular response to reloading appears to be closely related to intramuscular stimuli that are activated by mechanical loading (20,21,41,47,59) and/or muscle activation with reloading (1,12,20,22,41).Macrophage colony-stimulating factor (M-CSF, CSF-1) is a cytokine that influences hematopoietic stem cells to differentiate into macrophages and other cell types (54). Deficiency of macrophages has been well-reported in osteopetrotic (op/op) mutant mice with inactivating mutation of M-CSF gene, which results in the absence of certain macrophage and in osteopetrosis, following a lack of osteoclasts (60, 63). Tidball and Wehling-Henricks (58) reported important roles of macrophages in the repair of muscle fiber membrane, regeneration, and regrowth after unloading-related atrophy in mouse s...

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Macrophages in Injured Skeletal Muscle: A Perpetuum Mobile Causing and Limiting Fibrosis, Prompting or Restricting Resolution and Regeneration

Cited by 67 publications

References 162 publications

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Cell death, clearance and immunity in the skeletal muscle

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers

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