Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury

Emmeran Le Moal (1, 2) , G. Juban (1) , Anne-Sophie Bernard (3, 4) , T. Varga (5) , C. Policar (3, 4) , B. Chazaud (1) , R. Mounier (1)

1 INMG - Institut NeuroMyoGène
2 M2S - Laboratoire Mouvement Sport Santé
3 LBM UMR 7203 - Laboratoire des biomolécules
4 LBM UMR 7203 - Laboratoire des biomolécules
5 University of Debrecen Egyetem [Debrecen]

Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle.

Keywords: Tissue repair; Sterile inflammation; Oxidative stress

Domains: Biochemistry, Molecular Biology

Emmeran Le Moal, G. Juban, Anne-Sophie Bernard, T. Varga, C. Policar, et al.. Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury. Free Radical Biology and Medicine, 2018, 120, pp.33-40. ⟨10.1016/j.freeradbiomed.2018.02.024⟩. ⟨hal-01783729⟩