Abstract
Lactic acid (LA) is a sensitive indicator of exercise intensity and duration. A single bout of prolonged and intensive exercise can cause transient immunosuppression through the interaction of cellular, humoral, and hormone factors. Exercise-induced influences on neutrophil extracellular traps (NETs) release have been reported, but the underlying mechanism is unknown. This study investigated NETs release, cell-free DNA (cf-DNA), and LA concentration in mice after 60 and 145 min of intensive, graded treadmill running. The concentration of LA and cf-DNA increased, while the level of myeloperoxidase-DNA (MPO-DNA) (an indicator of NETs release) decreased during 145 min of exhaustive running. LA was positively and negatively correlated with cf-DNA and MPO-DNA (R2 = 0.57 and 0.53, respectively, both p < 0.001). Subsequent in vitro experiments were conducted with neutrophils activated by phorbol myristate acetate (PMA) in the presence of LA at different concentrations. Increasing LA concentrations were associated with decreases in NETs release and reactive oxygen species (ROS) formation. Taken together, this work furthers our understanding of how NETs and oxidative reaction respond to one bout of prolonged and intensive running. The data support a negative relationship between LA accumulation and NETs release after heavy exertion.
Highlights
A single, acute bout of prolonged, strenuous exercise has a temporary depressive effect on immune function including cell-mediated immunity, hormonal-mediated immunity, and hormonal changes (Nieman et al, 1989, 1993; Gleeson, 2007)
neutrophil extracellular traps (NETs) are capable of entrapping exogenous bacteria, allowing neutrophils to kill while minimizing damage to host cells
The NETs activation and release process (NETosis) begins with nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation of protein-arginine deiminase 4 (PAD4) via reactive-oxygen species (ROS), followed by chromatin decondensation aided by granule protein such as myeloperoxidase (Beck et al, 1999) and neutrophil elastase (NE) (Fuchs et al, 2007; Steinberg and Grinstein, 2007)
Summary
A single, acute bout of prolonged, strenuous exercise has a temporary depressive effect on immune function including cell-mediated immunity, hormonal-mediated immunity, and hormonal changes (Nieman et al, 1989, 1993; Gleeson, 2007). Beither et al showed an acute and transient increase in cf-DNA and neutrophils displaying morphological signs of NETs release in both endurance-trained and healthy sedentary individuals after 60 min of intensive cycling. Syu et al reported that intensive cycling bouts facilitated NETs formation in sedentary but not active subjects. Study methods did not include levels of the MPO-DNA complex, a more direct indicator of NETs production. To extend scientific understanding in this area, we designed a study to identify the impact of exercise on NETs formation using direct method, with an emphasis on underlying mechanisms including the potential effect of lactic acid. This study investigated NETs release, cf-DNA, MPO-DNA, and LA concentrations in mice after 60 and 145 min of intensive, graded treadmill running to a state of exhaustion. The correlation between LA concentration and NETs formation along with the underlying mechanism were explored
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