Macrophages in acute and chronic muscle damage. The innate immune system through M1 macrophages activates an inflammatory response: secretion of cytokines triggers the clearance of the tissue from the debris and the activation of stem cells. Phagocytosis of apoptotic and necrotic cells induces an M1 to M2 macrophage transition (I). M2 polarized macrophages originate from resident macrophages (II) or can be recruited from circulating monocyte (III). This is a regenerative stage during which stem cells differentiate and the damage is resolved. In chronic diseases several rounds of damage and repair occur: both M1 and M2 polarized macrophages coexist in the tissue, recruited from monocytes. This persistent inflammation leads to fibrosis, fat deposition, and exhaustion of the stem cell pool.
