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Optimal repair of skeletal muscle following injury requires a significant and well orchestrated inflammatory response. The infiltration of leukocytes, and particularly monocytes/macrophages, in the hours/days following injury is a critical component in the repair of skeletal muscle (Chazaud et al., 2009; Koh & Pizza, 2009). These cells are not only responsible for the clearance of cellular debris, but also the release of factors that help to control the myogenic program of stem cells (Chazaud et al., 2009). While the appearance and functions of these cells have been widely investigated, the factors that are responsible for the recruitment and chemotaxis of leukocytes into skeletal muscle are still somewhat unknown. Our aim was to investigate the effect of a single bout of resistance exercise on the expression and localization of 2 major chemoattractive factors, monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8).
Eight young males (22.1±0.2yr) completed three sets of resistance exercise for the leg muscles (leg press, leg extension and squat). Two sets consisted of 8-12 repetitions at 80% 1-RM, whereas in the final set the subjects exercised until exhaustion. Muscle biopsies were obtained before exercise, and 2, 4 and 24 h after exercise. Expression of MCP-1 and IL-8 was analyzed via Multiplex analysis (protein) and PCR (gene). Immunohistochemistry was used to establish localization.
Large increases in both gene and protein expression of MCP-1 and IL-8 were evident 2 h following exercise completion, returning to resting levels by 24 h. Neither factor was prevalent within the cytoplasm of myofibres following exercise. MCP-1 was localized predominately to Pax7 and CD68 positive mononucleated cells, but not strictly confined to these cell types. The distribution of IL-8 immunoreactivity was different to that of MCP-1 and seemed to be in close proximity to collagen IV expressing cells.
Both MCP-1 and IL-8 have been identified as major regulators of muscle mediated leukocyte recruitment in vitro (Chazaud et al., 2003; Peterson & Pizza, 2009). The present study indicated that both factors increased dramatically in response to a single bout of resistance exercise, which is in accordance with previous literature (Nieman et al., 2004; Hubal et al., 2008). The localization of these factors within a variety of cell types, and the contrasting pattern of expression, suggest a complex and multifaceted response occurs within the muscular microenvironment to regulate inflammation and muscular repair in response to resistance exercise.
Chazaud B, Brigitte M, Yacoub-Youssef H, Arnold L, Gherardi R, Sonnet C, Lafuste P & Chretien F. (2009). Dual and beneficial roles of macrophages during skeletal muscle regeneration. Exercise and Sport Sciences Reviews 37, 18-22.
Chazaud B, Sonnet C, Lafuste P, Bassez G, Rimaniol AC, Poron F, Authier FJ, Dreyfus PA & Gherardi RK. (2003). Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. Journal of Cell Biology 163, 1133-1143.
Hubal MJ, Chen TC, Thompson PD & Clarkson PM. (2008). Inflammatory gene changes associated with the repeated-bout effect. American Journal of Physiology. Regulatory, Integrated and Comparative Physiolopgy 294, R1628-1637.
Koh TJ & Pizza FX. (2009). Do inflammatory cells influence skeletal muscle hypertrophy? Frontiers in Bioscience (Elite Ed) 1, 60-71.
Nieman DC, Davis JM, Brown VA, Henson DA, Dumke CL, Utter AC, Vinci DM, Downs MF, Smith JC, Carson J, Brown A, McAnulty SR & McAnulty LS. (2004). Influence of carbohydrate ingestion on immune changes after 2 h of intensive resistance training. Journal of Applied Physiology 96, 1292-1298.
Peterson JM & Pizza FX. (2009). Cytokines derived from cultured skeletal muscle cells after mechanical strain promote neutrophil chemotaxis in vitro. Journal of Applied Physiology 106, 130-137.