Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity

Abstract

A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.

Figure 1. Cortisol (A) and interleukin-6 (IL-6; B) kinetics in the peripheral blood before and after an ergometry under normoxic and hypoxic conditions.

Data are reported as means ± SD. Plasma cortisol significantly increased 10 min post-exercise and dropped below baseline values 120 min post-exercise under both conditions (** p<0.01, normoxia: grey, hypoxia: black). Kinetics are parallel to those of circulating hematopoietic stem and progenitor cells (CPCs) . Interleukin-6 showed a time-delayed increase 30 min post-exercise under normoxia, whereas under hypoxic conditions values were already significantly elevated 10 min post-exercise. (* p<0.05, normoxia: grey, hypoxia: black).

Figure 2. Correlation analysis of free norepinephrine (free NE) to circulating hematopoietic stem and progenitor cell count (CPC,[6]) under normoxic and hypoxic conditions (NE sampled pre, directly after; CPCs sampled pre, 10 min post; n = 20); Sampling points were the rest and peak points of the two parameters.

The increase in CPCs is strongly correlated with a preceding increase in free NE.

Figure 3. Box-plot statistics (n = 6) of the in vitro influence of ergometry-induced norepinephrine (NE) concentrations (5*10⁻⁸ mol/l) on circulating hematopoietic stem and progenitor cell (CPC) proliferative capacity/functionality compared to NE resting values (5*10⁻⁹ mol/l) and a control group (no NE); data are expressed as area under the curve (AUC).

CPC functionality was significantly decreased under ergometry-induced NE concentrations when compared to resting values (* p<0.05). No significant change was seen comparing resting NE concentrations and a control group.

Figure 4. Box-plot statistics (n = 6) of the in vitro influence of ergometry-induced concentrations of norepinephrine (NE) and NE + lactate (NE: 5*10⁻⁸ mol/l; La: 12 mmol/l) on circulating hematopoietic stem and progenitor cell proliferative capacity/functionality expressed as area under the curve (AUC).

Circulating hematopoietic stem and progenitor functionality was not significantly altered under the influence of both parameters, but a decreasing trend could be detected (p = 0.08).