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. We investigated whether ASE exerted differential effects on NET formation in sedentary and physically active subjects. 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). 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. ASE in sedentary but not active subjects facilitated NET formation via elevating the NADPH oxidase-generated ROS and suppressing the ΔΨm.