Abstract
Neutrophil spontaneous apoptosis, a process crucial for immune regulation, is mainly controlled by alterations in reactive oxygen species (ROS) and mitochondria integrity. Exercise has been proposed to be a physiological way to modulate immunity; while acute severe exercise (ASE) usually impedes immunity, chronic moderate exercise (CME) improves it. This study aimed to investigate whether and how ASE and CME oppositely regulate human neutrophil apoptosis. Thirteen sedentary young males underwent an initial ASE and were subsequently divided into exercise and control groups. The exercise group (n = 8) underwent 2 months of CME followed by 2 months of detraining. Additional ASE paradigms were performed at the end of each month. Neutrophils were isolated from blood specimens drawn at rest and immediately after each ASE for assaying neutrophil spontaneous apoptosis (annexin-V binding on the outer surface) along with redox-related parameters and mitochondria-related parameters. Our results showed that i) the initial ASE immediately increased the oxidative stress (cytosolic ROS and glutathione oxidation), and sequentially accelerated the reduction of mitochondrial membrane potential, the surface binding of annexin-V, and the generation of mitochondrial ROS; ii) CME upregulated glutathione level, retarded spontaneous apoptosis and delayed mitochondria deterioration; iii) most effects of CME were unchanged after detraining; and iv) CME blocked ASE effects and this capability remained intact even after detraining. Furthermore, the ASE effects on neutrophil spontaneous apoptosis were mimicked by adding exogenous H2O2, but not by suppressing mitochondrial membrane potential. In conclusion, while ASE induced an oxidative state and resulted in acceleration of human neutrophil apoptosis, CME delayed neutrophil apoptosis by maintaining a reduced state for long periods of time even after detraining.
Highlights
Neutrophils play a critical role in the first line of defense against pathogens
This study is the first to show that acute severe exercise (ASE) and chronic moderate exercise (CME) differentially affect human neutrophil apoptosis and redox balance
ASE accelerated neutrophil apoptosis, while CME damped it
Summary
Neutrophils play a critical role in the first line of defense against pathogens. They rapidly migrate to the infection site, ingest the pathogens, release reactive oxygen species (ROS) to kill the pathogens, and even release their own DNA to form extracellular traps [1]. Regulation of neutrophil life span by spontaneous apoptosis has for a long time been considered to be a major way of optimizing innate immunity under healthy conditions. There are three lines of evidence supporting that ROS limits the neutrophil lifespan. Neutrophil glutathione (GSH, a major antioxidant in mamalian cells) decreases over time, results in ROS accumulation, and limits neutrophil lifespan [10]. Apoptotic neutrophils are functionally compromised because their stimulation-evoked responses, such as spreading, chemotaxis and oxidative burst, are either completely absent or greatly reduced [12]
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