Hypoxic exercise training promotes anti-tumor cytotoxicity of natural killer cells in men

Clinical Science (2011) Immediate Publication, doi:10.1042/CS20110032 Hypoxic exercise training promotes anti-tumor cytotoxicity of natural killer cells in menJong-Shyan Wang and Tzu-Pin WengGraduate Institute of Rehabilitation Science, Chang Gung University, Tao-Yuan 333, Taiwan. s5492@mail.cgu.edu.twThe cytotoxic functions of natural killer cells (NKs) are critical in enabling the immune system to cope efficiently with malignancy. This investigation compared how various exercise regimens with/without hypoxia influence phenotypic characteristics of NK subsets and cytotoxicity of NKs to nasopharyngeal carcinoma cells (NPCs). Sixty sedentary males were randomly divided into five groups. Each group (n=12) underwent one of five interventions: normoxic (21%O2) resting, hypoxic (15%O2) resting, normoxic exercise (50% maximal work-rate under 21%O2, N-E), hypoxic-relative exercise (50% maximal heart rate reserve under 15%O2, H-RE), or hypoxic-absolute exercise (50% maximal work-rate under 15%O2, H-AE) for 30 minutes/day, five days/week for four weeks. The results showed that hypoxic exercise regimens increased pulmonary ventilation and tissue oxygen utilization. Moreover, H-RE enhanced aerobic fitness at a less intensive training workload than H-AE. Before each intervention, strenuous exercise elevated NK perforin/granzyme B contents and promoted cytotoxicity of NKs to NPCs. However, the percentages of NKs-expressing homing (CD11a)/terminally differentiated (CD57)/inhibitory (KLRG1) molecules that entered the bloodstream from peripheral tissues increased following this exercise. After four weeks of interventions, both H-AE and H-RE up-regulated the memory (CD45RO)/activating (NKG2D) expressions and were accompanied by the decreases in the CD57/KLRG1 levels on NKs at rest and after strenuous exercise. Furthermore, the two regimens increased resting and exercise NK perforin/granzyme B contents and NK-induced phosphatidylserine exposure of NPCs. In contrast, no significant change in phenotypic characteristics of blood NK subsets or NK-induced NPC apoptosis was observed following the N-C, H-C, and N-E. Therefore, we conclude that 15%O2 exercise training reduces terminally differentiated NK subsets and up-regulates the expressions of activating molecules and cytotoxic granule proteins of NKs, thereby enhancing capacity of anti-NPC cytotoxicity by NKs. These findings can help to determine effective hypoxic exercise regimens for improving individual aerobic capacity and simultaneously promoting the natural cytotoxicity of NKs.

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