Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo (original) (raw)
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Altered Macrophage Phenotype Transition Impairs Skeletal Muscle Regeneration
The American Journal of Pathology, 2014
Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11bdiphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b þ (CD90/B220/CD49b/NK1.1/Ly6G) À (F4/80/I-Ab/CD11c) À Ly6C þ/À ] accumulation occurred; interestingly, Ly6C þ and Ly6C À monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C þ macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b þ F4/80 þ cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b þ F4/80 þ Ly6C À CD301 À macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of antiinflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C À macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration. (Am J Pathol 2014, 184: 1167e1184; http://dx.
Dual and Beneficial Roles of Macrophages During Skeletal Muscle Regeneration
Exercise and Sport Sciences Reviews, 2009
Macrophages are necessary for skeletal muscle regeneration after injury. Muscle recruits inflammatory monocytes/macrophages that switch toward an anti-inflammatory profile upon phagocytosis of debris. In vitro, proinflammatory macrophages stimulate myoblast proliferation, whereas anti-inflammatory macrophages stimulate their differentiation. Thus, macrophages are involved in both phases of skeletal muscle regeneration: first, inflammation and cleansing of necrosis, and then myogenic differentiation and tissue repair.
Macrophage plasticity in skeletal muscle repair
2014
Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.
Journal of Applied Physiology, 2012
Skeletal muscle is one of the most sensitive tissues to mechanical loading, and unloading inhibits the regeneration potential of skeletal muscle after injury. This study was designed to elucidate the specific effects of unloading stress on the function of immunocytes during muscle regeneration after injury. We examined immunocyte infiltration and muscle regeneration in cardiotoxin (CTX)-injected soleus muscles of tail-suspended (TS) mice. In CTX-injected TS mice, the cross-sectional area of regenerating myofibers was smaller than that of weight-bearing (WB) mice, indicating that unloading delays muscle regeneration following CTX-induced skeletal muscle damage. Delayed infiltration of macrophages into the injured skeletal muscle was observed in CTX-injected TS mice. Neutrophils and macrophages in CTX-injected TS muscle were presented over a longer period at the injury sites compared with those in CTX-injected WB muscle. Disturbance of activation and differentiation of satellite cells...
Macrophage Therapy Activates Endogenous Muscle Stem Cells and Accelerates Muscle Regeneration
2020
Background: The effects of macrophage therapies on muscle regeneration and stem cell activation after injury remains unclear. This study aims to know the effect of macrophage therapies on muscle l regeneration and endogenous stem cell activation towards new muscleMethods: Adult male Swiss mice were subjected to an injury in the gastrocnemius, close to the myotendinous junction, using a 2-mm biopsy tube. Animals were assigned to the following groups: 1.- Injury; 2.- Injury+ clodronate. Macrophages were depleted 24 hours after injury by clodronate injection. 3. - Injury+ clodronate+ macrophage therapy. Macrophage depleted mice were treated with an intramuscularl injection of 1 million peritoneal macrophages modified with intermittent anoxia reoxygenation. Animals were sacrificed at 4, and 15 days after the injury, (n = 8 per study time). Gene expression of proliferating cell nuclear antigen(PCNA) and Ki67 as cell proliferating markers, mannose receptor Ecotype 1(MRC1) and Interleukin1...
Macrophage Plasticity and the Role of Inflammation in Skeletal Muscle Repair
Mediators of Inflammation, 2013
Effective repair of damaged tissues and organs requires the coordinated action of several cell types, including in�ltrating in�ammatory cells and resident cells. Recent �ndings have uncovered a central role for macrophages in the repair of skeletal muscle aer acute damage. If damage persists, as in skeletal muscle pathologies such as Duchenne muscular dystrophy (DMD), macrophage in�ltration perpetuates and leads to progressive �brosis, thus exacerbating disease severity. Here we discuss how dynamic changes in macrophage populations and activation states in the damaged muscle tissue contribute to its efficient regeneration. We describe how ordered changes in macrophage polarization, from M1 to M2 subtypes, can differently affect muscle stem cell (satellite cell) functions. Finally, we also highlight some of the new mechanisms underlying macrophage plasticity and brie�y discuss the emerging implications of lymphocytes and other in�ammatory cell types in normal versus pathological muscle repair.
The Journal of physiology, 2017
The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of i...
Monocyte depletion increases local proliferation of macrophage subsets after skeletal muscle injury
BMC Musculoskeletal Disorders, 2013
Background: Sequential accumulation of M1 and M2 macrophages is critical for skeletal muscle recovery after an acute injury. While M1 accumulation is believed to rely on monocyte infiltration, the mechanisms of M2 accumulation remain controversial, but could involve an infiltrating precursor. Yet, strong depletion of monocytes only partially impairs skeletal muscle healing, supporting the existence of alternative mechanisms to palliate the loss of infiltrating macrophage progenitors. The aims of this study are thus to investigate if proliferation occurs in macrophage subsets within injured skeletal muscles; and to determine if monocyte depletion leads to increased proliferation of macrophages after injury. Methods: Injury was induced by bupivacaine injection in the tibialis anterior muscle of rats. Blood monocytes were depleted by daily intravenous injections of liposome-encapsulated clodronate, starting 24 h prior to injury. In separate experiments, irradiation of hind limb was also performed to prevent resident cell proliferation. Upon euthanasia, blood and muscles were collected for flow cytometric analyses of macrophage/monocyte subsets.
Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF
Stem Cell Research & Therapy, 2020
Background After traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. The sequence of M1 and M2 macrophage accumulation and the duration of each subtype in the injured area may help to direct the relative extent of fibrogenesis and myogenesis during healing. We hypothesized that increasing the number of M1 macrophages early after traumatic muscle injury would produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing. Methods To test this hypothesis, we transfected skeletal muscle with a plasmid vector to transiently express GM-CSF shortly after injury to drive the polarization of macrophages towards the M1 subset. C57BL/6 mouse tibialis anterior (TA) muscles were injured by contusion and electroporated with uP-mGM, which is a plasmid vector that transiently expresses GM-CSF. Myogenesis, angiogenesis, and fibrosis were evaluated by histology, immunohistochemistry, ...
Macrophages and skeletal muscle regeneration: a clodronate-containing liposome depletion study
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006
The study evaluates the influence of monocytes/macrophages in the mechanisms of skeletal muscle injury using a mouse model and selective depletion of peripheral monocyte with systemic injections of liposomal clodronate (dichloromethylene bisphosphonate). This pharmacological treatment has been demonstrated to induce specific apoptotic death in monocytes and phagocytic macrophages. In the current studies, the liposomal clodronate injections resulted in a marked attenuation of the peak inflammatory response in the freeze-injured muscle in the first three days after injury.