Fig. 4.

Summary of general interactions between immune cells and muscle cells following acute muscle injury (A) or during chronic muscle injury that occurs in mdx dystrophy (B). A: acute damage causes release of chemoattractant molecules that initially attract neutrophils (PMNs) or M1 macrophages (M1) into the muscle. Neutrophils and M1 macrophages promote further damage through nitric oxide (NO)-mediated processes. M1 macrophages also release cytokines that can promote satellite cell activation and proliferation. Neutrophils and M1 macrophages are then replaced by M2 macrophages that then promote muscle repair, differentiation and growth. B: during chronic muscle injury, the initial inflammatory response is similar to the response to acute damage, typified by neutrophil and M1 macrophage invasion. However, M2a macrophages invade contemporaneously and inhibit NO-mediated lysis by M1 macrophages and promote muscle fibrosis through arginase metabolism of arginine. M2 macrophages may also participate in activation of cytotoxic T-cells that are then able to promote muscle damage through perforin-mediated processes. The Th2 inflammatory environment also increases the activation of eosinophils (EOS) that contribute to muscle lysis through major basic protein-1 (MBP-1) mediated lysis. Eosinophils also increase muscle fibrosis through MBP-dependent processes and negatively regulate the cellular immune response to chronically injured muscle.