Abstract
PurposePhysical exercise is reported to affect the immune response in various ways. Thus, the levels of pro-inflammatory cytokines as well as the abundance of circulating leukocytes are changed. In this study, the occurence of circulating cell-free mitochondrial DNA (cfmtDNA) and nuclear DNA (nDNA) was investigated in connection with a single bout of strenuous physical exercise.MethodsHealthy volunteers performed a controlled ergo-spirometry cycle test and venous blood samples were taken at different time-points to analyze the concentration of blood components before, during and after the test. The number of circulating leukocytes was measured, as well as secretion of the soluble urokinase activator receptor (suPAR).ResultsCf-mtDNA significantly increased during exercise, compared to baseline values and after 30 and 90 min of rest. Circulating leukocytes increased during exercise, but returned to baseline levels afterwards. Surface expression of the urokinase plasminogen activating receptor (uPAR) on neutrophils decreased significantly during exercise. The concentration of suPAR tended to increase during exercise but only significantly after 90 min of rest.ConclusionIncreased concentration of cf-mtDNA indicates that cell damage takes place during high intensity training. Hypoxia and tissue damage are likely causes of cf-mtDNA from muscle cells. The levels of cf-mtDNA remain high during the initial rest, due to the decreasing numbers of leukocytes normally clearing the plasma from cf-mtDNA. The increased levels of suPAR further emphasize that strenuous physical exercise causes a reaction similar to inflammation. Further studies are needed to detect the source of increased cf-mtDNA and the corresponding increase of suPAR liberation.
Highlights
The effect of strenuous physical exercise on the immune system has been studied during the last years
In case of cellular damage, endogenous cellular substances normally not exposed to the immune system, act as danger-associated molecular patterns (DAMPs), as they are released into the circulation
This study was performed to investigate if a single bout of strenuous physical exercise affects the concentration of cell-free mitochondrial DNA (cfmtDNA) and soluble urokinase plasminogen activating receptor (suPAR) in plasma
Summary
The effect of strenuous physical exercise on the immune system has been studied during the last years. In case of cellular damage, endogenous cellular substances normally not exposed to the immune system, act as danger-associated molecular patterns (DAMPs), as they are released into the circulation These molecules are recognized by different pattern recognition receptors, such as Toll-like receptors (TLRs), on immune cells causing a signaling cascade leading to excretion of antimicrobial substances and pro-inflammatory substances (Zhang et al 2010a, b). Mitochondrial DNA (mtDNA), released into circulation from mitochondria under stress, has been reported to act as a DAMP, mimicking an ongoing immune-activation, mediating a pro-inflammatory response (Bhagirath et al 2015; Chiu et al 2003; Yu 2012). Due to muscle damage, necrosis and oxygen deprivation has been shown to result in immune-activation resembling trauma and sepsis, the contribution of mitochondrial function has to be taken into account. Studies of trauma have revealed that inflammation, neutrophil activation and organ injury can be mediated by cell free mtDNA (cf-mtDNA) activating neutrophils via TLR-9, normally binding bacterial DNA (Zhang et al 2010a, b)
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