Acute severe exercise facilitates neutrophil extracellular trap formation in sedentary but not active subjects

Neutrophil extracellular trap (NET), a newly revealed antimicrobial strategy, is usually evoked by reactive oxygen species (ROS) and nicotinamide adenine denucleotide phosphate (NADPH) oxidase activation. In addition, the acute severe exercise (ASE)-induced oxidative stress in neutrophils depends on the subject's physical fitness. Purpose: We investigated whether ASE exerted differential effects on NET formation in sedentary and physically active subjects. Methods: Young males, 10 sedentary and 10 physically active, underwent an ASE (pedaling on a bicycle ergometer with increasing loads until exhaustion). Neutrophils were isolated from blood specimens drawn before and immediately after ASE for assaying NET formation along with redox-related parameters and mitochondrial membrane potential (ΔΨm). Results: In the sedentary group, 1) after ASE, NET formation increased spontaneously and in response to stimulation with phorbol 12-myristate 13-acetate; 2) ASE increased cytosolic ROS, decreased glutathione, and suppressed ΔΨm in neutrophils; 3) removing ROS or inhibiting NADPH oxidase prevented the ASE-facilitated NET formation; and 4) suppressing ΔΨm prevented the ASE-facilitated NET formation. On the contrary, these ASE effects on neutrophils did not happen in the active group. Conclusions: ASE in sedentary but not active subjects facilitated NET formation via elevating the NADPH oxidase-generated ROS and suppressing the ΔΨm.