Regulatory interactions between muscle and the immune system during muscle regeneration

Abstract

Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol 298: R1173-R1187, 2010. First published March 10, 2010 doi:10.1152/ajpregu.00735.2009.-Recent discoveries reveal complex interactions between skeletal muscle and the immune system that regulate muscle regeneration. In this review, we evaluate evidence that indicates that the response of myeloid cells to muscle injury promotes muscle regeneration and growth. Acute perturbations of muscle activate a sequence of interactions between muscle and inflammatory cells. The initial inflammatory response is a characteristic Th1 inflammatory response, first dominated by neutrophils and subsequently by CD68 ϩ M1 macrophages. M1 macrophages can propagate the Th1 response by releasing proinflammatory cytokines and cause further tissue damage through the release of nitric oxide. Myeloid cells in the early Th1 response stimulate the proliferative phase of myogenesis through mechanisms mediated by TNF-␣ and IL-6; experimental prolongation of their presence is associated with delayed transition to the early differentiation stage of myogenesis. Subsequent invasion by CD163ϩ /CD206 ϩ M2 macrophages attenuates M1 populations through the release of anti-inflammatory cytokines, including IL-10. M2 macrophages play a major role in promoting growth and regeneration; their absence greatly slows muscle growth following injury or modified use and inhibits muscle differentiation and regeneration. Chronic muscle injury leads to profiles of macrophage invasion and function that differ from acute injuries. For example, mdx muscular dystrophy yields invasion of muscle by M1 macrophages, but their early invasion is accompanied by a subpopulation of M2a macrophages. M2a macrophages are IL-4 receptor ϩ /CD206 ϩ cells that reduce cytotoxicity of M1 macrophages. Subsequent invasion of dystrophic muscle by M2c macrophages is associated with progression of the regenerative phase in pathophysiology. Together, these findings show that transitions in macrophage phenotype are an essential component of muscle regeneration in vivo following acute or chronic muscle damage. skeletal muscle; macrophage; neutrophil; muscular dystrophy; chemokines SKELETAL MUSCLE HAS A REMARKABLE capacity for repair, even following severe damage. Experimental findings show that crushing muscle, killing muscle by the injection of toxins, mechanical destruction caused by large, lengthening stretches, or killing muscle fibers by freezing can be followed by the successful regeneration of muscle that leads to recovery of normal structure and function. The regenerative capacity of skeletal muscle relies largely on the presence of a population of mononucleated, myogenic cells, called satellite cells, that retain their ability to proliferate and then differentiate to either fuse with existing fibers or with other myogenic cells to generate new fibers. Thus, perturbations to the processes that normally regulate the activation, proliferat...

Skeletal muscle regeneration involves macrophage-myoblast bonding

“…This capacity relies on the existence of a local population of myogenic cells that are readily activated by local cues and start their proliferation and subsequent differentiation. The intervention of the initial inflow of inflammatory cells in the regulation of regeneration was long discussed and analyzed 6 up to being declared indispensable. 9 Meddling with the inflammatory response after acute injury proved detrimental to tissue healing.…”

“…4 Similar kinetics of macrophage subtypes and adult myogenesis sequences were demonstrated during normal regeneration in human samples. 5 Though, most studies looking at the involvement of macrophages in the regeneration process have focused on soluble molecules like prostaglandins, cytokines and chemokines, 6 only few reports assumed the importance of intercellular contacts. Sonnet et.…”

Photobiomodulation and different macrophages phenotypes during muscle tissue repair

“…M1 cell surface marker CD68 is a receptor for oxidized low‐density lipoproteins that activate phagocytosis and increase the production of proinflammatory cytokines when specifically connected. Normal muscle tissue does not express CD68 + macrophages 3, 4…”

“…M2 macrophages produce anti‐inflammatory cytokines and growth factors as TGF‐ β and IL‐10 as well as enzymes that are important to angiogenesis, fibroblast proliferation and the differentiation of myogenic precursor cells 1, 4, 5. M2 macrophage surface marker CD206 is a mannose receptor that internalizes sugar moieties on molecules in inflamed tissue, such as myeloperoxidase 3. CD163 is a specific receptor for hemoglobin and haptaglobin complexes 3.…”

“…M2 macrophage surface marker CD206 is a mannose receptor that internalizes sugar moieties on molecules in inflamed tissue, such as myeloperoxidase 3. CD163 is a specific receptor for hemoglobin and haptaglobin complexes 3. Specific binding to the both receptors triggers the expression of anti‐inflammatory cytokines, such as IL‐10 and TGF‐ β, leading to the deactivation of M1 macrophages1, 3, 4 and enabling the predominance of M2 macrophages at the injury site during the transition from the proliferative stage to the differentiation and growth stage of myogenesis 1, 3, 4…”