Exercise affects tissue lymphocyte apoptosis via redox-sensitive and Fas-dependent signaling pathways

Kruger K, Frost S, Most E, Volker K, Pallauf J, Mooren FC. Exercise affects tissue lymphocyte apoptosis via redox sensitive and Fas-dependent signaling pathways. Am J Physiol Regul Integr Comp Physiol 296: R1518-R1527, 2009. First published March 4, 2009; doi:10.1152/ajpregu.90994.2008.-Intensive and exhaustive exercise induces an activation of blood T-lymphocytes, which seems to be terminated by apoptotic processes in the postexercise period. Here, we report that exercise-induced T-lymphocyte apoptosis is a systemic phenomenon occurring in various lymphoid and nonlymphoid tissues. The apoptosis rate could be related to exercise intensity and type. Although in some tissues, such as the spleen and Peyer's patches, an early start of apoptosis (1-3 h postexercise) could be detected, a delayed apoptosis (24 h postexercise) was observed in lung, bone marrow, and lymph nodes. Further analysis showed a similar apoptosis distribution among lymphocyte subpopulations. We tested whether components of the extrinsic or the intrinsic apoptotic pathways or both were involved in these processes. Elevated levels of lipid peroxidation-product malondialdehyde (MDA), indicating an increased production of reactive oxygen species (ROS), were found after exercise in Peyer's patches, lung, and spleen, but not in lymph nodes. Application of N-acetyl-cysteine (NAC) prevented exercise-induced T-cell apoptosis completely in spleen and bone marrow, partially in lung and Peyer's patches, while it was ineffective in lymph nodes. Additionally, exercise addressed the Fas-mediated apoptosis. The percentage of Fas-receptor (Fas +) and Fas-ligand positive (FasL +) lymphocytes was enhanced in Peyer's patches after exercise. Moreover, FasL + T cells were increased in the lung, while in lymph nodes Fas + cells were increased. The critical role of Fas signaling in exercise-induced apoptosis was supported by using Fas-deficient MRL/lpr-mice. In Fas-deficient mice, exercise-induced T-lymphocyte apoptosis was prevented in spleen, lung, bone marrow, and lymph nodes, but not in Peyer's patches. These data demonstrate that exercise-induced lymphocyte apoptosis is a transient systemic process with tissue-type specific apoptosis-inducing mechanisms, whose relevance for the adaptive immune competence remains to be shown.