Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise

Abstract

Exhaustive exercise promotes muscle injury, including myofiber lesions; however, its exact mechanism has not yet been elucidated. In this study, we tested the hypothesis that macrophage depletion by pretreatment with clodronate liposomes alters muscle injury and inflammation following exhaustive exercise. Male C57BL/6J mice were divided into four groups: rest plus control liposome (n=8), rest plus clodronate liposome (n=8), exhaustive exercise plus control liposome (n=8), and exhaustive exercise plus clodronate liposome (n=8). Mice were treated with clodronate liposome or control liposome for 48 h before undergoing exhaustive exercise on a treadmill. Twenty-four hours after exhaustive exercise, the gastrocnemius muscles were removed for histological and PCR analyses. Exhaustive exercise increased the number of macrophages in the muscle; however, clodronate liposome treatment reduced this infiltration. Although exhaustive exercise resulted in an increase in injured myofibers, clodronate liposome treatment following exhaustive exercise reduced the injured myofibers. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the skeletal muscle after exhaustive exercise. These results suggest that macrophages play a critical role in increasing muscle injury by regulating inflammation.

Effects of transforming growth factor‐β1 treatment on muscle regeneration and adipogenesis in glycerol‐injured muscle

“…For immunohistochemistry, sections were incubated with rabbit anti‐α smooth muscle actin (SMA) antibody (1:200, NB600‐531; Novus Biologicals) and rabbit anti‐F4/80 antibody (1:500, sc‐26643‐R; Santa Cruz) for detection of myofibroblasts and macrophages (Kawanishi et al . ), respectively. Immunoreactivity was detected with 3,3′‐diaminobenzidine (DAB) (Dako).…”

Cytokine Response to Exercise and Its Modulation

“…Also, IL-6 and G-CSF are involved in neutrophil mobilization from bone marrow reserves to the circulation after exercise [ 6 , 7 , 13 ]. Although neutrophils are involved in exercise-induced muscle damage and inflammation, we recently demonstrated that neutrophils mobilized into muscle contribute to exacerbating muscle injury by upregulating proinflammatory cytokine expression through the induction of macrophage infiltration with MCP-1 [ 37 , 38 ]. From this point of view, leukocytosis (neutrophilia) and related variables noted above can be good predictive indicators of exhaustive exercise-induced muscle and other organ damage/dysfunction [ 1 ].…”

Involvement of Neutrophil Dynamics and Function in Exercise-Induced Muscle Damage and Delayed-Onset Muscle Soreness: Effect of Hydrogen Bath

“…Exercise-induced muscle damage (EIMD), which is one of the reasons for DOMS, is caused by not only mechanical factors, but also non-mechanical factors [3]. One possible mechanism causing muscle damage is the invasion of leukocytes, especially phagocytes, including neutrophils and macrophages, into skeletal muscle [4,5,6]. Phagocytes infiltrating muscle tissue play essential roles in tissue repair, such as protein degradation and removal of cellular debris, whereas activated phagocytes release pro-inflammatory cytokines and reactive oxygen species (ROS), and induce inflammation as well as myofiber membrane lysis [4,7].…”