Mechanisms of macrophages accumulation in the process of immobilized-induced muscle contracture in rats

Introduction/Background Skeletal muscle fibrosis is the main pathology of immobilized-induced muscle contracture. Our previous studies revealed that upregulation of interleukin-1β/transforming growth factor-β1 associated with macrophages accumulation was related to the development of skeletal muscle fibrosis. However, the mechanisms underlying the increase in the number of macrophages in the immobilized soleus muscle are unclear. In this study, we investigated the mechanisms of macrophages accumulation in the immobilized soleus muscle of rat ankle- joint contracture models. Material and method Rats were divided into immobilization and control groups. In the immobilization group, both ankle joints of each rats were immobilized in full plantar flexion with plaster casts for 1 and 2 weeks. To assess alterations of macrophages, the number of CD11b-positive cells and the monocyte chemotactic protein (MCP)-1 mRNA expression were measured. Additionally, to assess alterations of the myocyte, the number of myonuclei and TUNEL-positive cells, cross-sectional area (CSA) of myofibers, and the myonuclear domain size were measured. Results Immobilization resulted in a significant increase in the number of CD11b-positive cells and the MCP-1 mRNA expression at 1 and 2 weeks. The number of myonuclei and the CSA of myofibers were significantly decreased in the immobilization group compared to the control group at 1 and 2 weeks. Only the CSA of myofibers significantly decreased, depending on the immobilization period. The myonuclear domain size was significantly lower in the immobilization group at 2 weeks compared to the control group. TUNEL-positive cells were significantly increased in the immobilization group compared to the control group at 1 and 2 weeks. Conclusion These results indicated that joint immobilization after 1 week induced macrophages accumulation and reduced the number of myonuclei associated with myocyte apoptosis, which caused a decrease in the CSA of myofibers. These changes suggest that immobilized-induced muscle fiber atrophy following myocyte apoptosis induce macrophage accumulation.