Exercise-recruited NK cells display exercise-associated eHSP-70

It is hypothesized that increased plasma or serum concentrations of extracellular heat shock proteins (eHSP) serve as a danger signal to the innate immune system. Cellular binding of eHSP leads to activation of NK cells and monocytes, as measured by their increased cytokine production, mitotic division and killing capacity. We examined whether eHSP binds to NK lymphocytes in vivo in athletes performing endurance exercise in the heat. Eighteen trained male runners ran at 70% VO2max at 35 degrees C and 40% relative humidity. Venous blood collected before, after and 1.5 h after exercise was analysed for leukocyte distribution, phenotype and eHSP70. NK cell-enriched samples were examined for co-localization of CD94 and eHSP70 expression. Plasma eHSP-70 concentration was measured by ELISA. Subjects ran for approximately 50 min, which elicited a reversible leukocytosis. NK cell count increased 83% (p < 0.01) immediately after exercise, then decreased to 66% of the resting level 1.5 h after exercise (p < 0.05). Plasma eHSP concentration increased 167% after exercise and remained elevated (by up to 71%) 1.5 h after exercise (p < 0.01). eHSP was expressed on both NK cells and monocytes at all times; the count of NK cells positive for eHSP doubled from 0.04 +/- 0.02 10(9)/L (mean +/- SD) to 0.08 +/- 0.06 10(9)/L after exercise. In summary, exercise in the heat increased free plasma eHSP concentration, and the eHSP co-localized with CD94 on NK cells. These data confirm the link between exercise and activation of the innate immune system.