Role of macrophages during skeletal muscle regeneration and hypertrophy—Implications for immunomodulatory strategies

Abstract

Skeletal muscle is a plastic tissue that regenerates ad integrum after injury and adapts to raise mechanical loading/contractile activity by increasing its mass and/or myofiber size, a phenomenon commonly refers to as skeletal muscle hypertrophy. Both muscle regeneration and hypertrophy rely on the interactions between muscle stem cells and their neighborhood, which include inflammatory cells, and particularly macrophages. This review first summarizes the role of macrophages in muscle regeneration in various animal models of injury and in response to exercise-induced muscle damage in humans. Then, the potential contribution of macrophages to skeletal muscle hypertrophy is discussed on the basis of both animal and human experiments. We also present a brief comparative analysis of the role of macrophages during muscle regeneration versus hypertrophy. Finally, we summarize the current knowledge on the impact of different immunomodulatory strategies, such as heat therapy, cooling, massage, nonsteroidal anti-inflammatory drugs and resolvins, on skeletal muscle regeneration and their potential impact on muscle hypertrophy.

Kinetics of skeletal muscle regeneration after mild and severe muscle damage induced by electrically‐evoked lengthening contractions

“…After an injury, neutrophils are the first immune cells to invade the injury site where they attract monocytes and start the inflammatory response. 32,33 This could therefore explain the larger infiltration of macrophages after severe than mild damage, even though additional studies are needed to describe the kinetics of neutrophil infiltration after electrically-evoked LC. We also showed that the number of macrophages was not different between the two damaging protocols during the proliferating phase of MuSCs (i.e., from day 1 to day 3).…”

“…34 Although several pro-myogenic/trophic secreted factors from antiinflammatory/restorative macrophages (e.g., IGF-1, TGFβ, GDF3, etc.) 32 have been described during the regenerative inflammation phase of muscle repair after toxic injury, further investigations are needed to determine the influence of muscle damage severity on the inflammatory profile of macrophages.…”

“…This suggests that the recruitment of other immune cells, such as neutrophils, was larger after severe than mild injury. After an injury, neutrophils are the first immune cells to invade the injury site where they attract monocytes and start the inflammatory response 32,33 . This could therefore explain the larger infiltration of macrophages after severe than mild damage, even though additional studies are needed to describe the kinetics of neutrophil infiltration after electrically‐evoked LC.…”

How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?

“…The cellular environment of contractile fibers is highly complex and contains myogenic stem cells (MuSCs), mesenchymal stromal cells (MSCs), such as fibro/adipogenic progenitors (FAPs), and resident macrophages [ 204 , 205 , 206 ]. Muscle-specific satellite cells are positioned between the sarcolemma membrane and basal lamina.…”

The Involvement of Lipid Mediators in the Mechanisms of Exercise-Induced Muscle Damage

“…Though, accessing this process is difficult due to the multiple cells, mediators and pathways involved. This process and its resolution are driven by a complex set of mediators that regulates cellular events required to clear inflammatory cells from sites of infection and injury and the restoration of tissue function [4][5][6][7].…”