Inflammatory processes in muscle injury and repair

Abstract

Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.

Skeletal muscle regeneration involves macrophage-myoblast bonding

“…2 Following neutrophils, macrophages are the second cell population attracted at the injury site, where they release high amounts of enzymes, cytokines, chemokines and growth factors. Although macrophage subpopulations peak at 3 to 6 days, they are detected in high number even 2 weeks after extensive muscle damage.…”

Systemic cytokine response following exercise-induced muscle damage in humans

“…Exercise-induced muscle damage has been associated with disruption of the normal myofilament structures in sarcomeres (6), damage to sarcolemma, loss of fiber integrity and leakage of muscle-specific enzymes and proteins into the blood (7), acute inflammatory response (8)(9)(10)(11), delayed-onset muscle soreness and loss of muscle contraction force (12).…”

Can Cytoprotective Cobalt Protoporphyrin Protect Skeletal Muscle and Muscle-derived Stem Cells From Ischemic Injury?

“…These not only directly cause myocyte membrane lysis and cell death [39,41], but also contribute to the secondary systemic effects of traumatic injury on distant organs such as acute respiratory distress syndrome [9,27]. MPO-related cytotoxicity is influenced by the oxidative/nitrosative state of the tissue environment [39], which can be modulated by HO-1 through its potent antioxidant effects, catabolism of prooxidant free heme, and stabilization of mitochondrial function [2,10].…”

“…MPO-related cytotoxicity is influenced by the oxidative/nitrosative state of the tissue environment [39], which can be modulated by HO-1 through its potent antioxidant effects, catabolism of prooxidant free heme, and stabilization of mitochondrial function [2,10].…”