Macrophage Infiltration, Activation, and Therapeutic Implication in Skeletal Muscle Injury and Repair

Skeletal muscle injury triggers inflammatory response, of which the accumulation of intramuscular monocytes/macrophages is a prominent feature. Macrophages in injured muscle comprise both blood monocytes-derived infiltrating macrophages, which are recruited through CCR2 signaling, and pre-existing muscle resident macrophages, which are established during embryogenesis and maintained until adulthood through self-renewal proliferation. During regenerative acute muscle injury, infiltrating monocytes/macrophages are heterogeneously activated in a temporal dynamic, responding to the changing microenvironment in injured muscle and contributing to the complete injury repair. Injury-associated monocytes/macrophages recede with the completion of muscle injury repair. In contrast, injury-associated monocytes/macrophages persist in dystrophic muscle of Duchenne muscular dystrophy (DMD), likely accounting for persistent inflammation and progressive fibrosis of DMD muscle. We review here the current knowledge on monocyte/macrophage infiltration and activation in both acutely injured skeletal muscle and dystrophic muscle with subsequent discussion of the potential therapeutic implication in treating muscular dystrophy.