Exercise-Induced Norepinephrine Decreases Circulating Hematopoietic Stem and Progenitor Cell Colony-Forming Capacity

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.ISSN:1932-620

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.

<p>The increase in CPCs is strongly correlated with a preceding increase in free NE.</p

Correlations of exercise-induced plasma parameters to blood cell counts.

<p>Pearson's correlation analysis; Pearson's r and the according p-values are reported. Abbreviations: WBC, white blood cells; RBC, red blood cells; PLT, platelets; LYM, lymphocytes; NEU, neutrophils; significances are indicated as follows: **p<0.01, *p<0.05</p><p>Correlations of exercise-induced plasma parameters to blood cell counts.</p

Free/bound epinephrine levels (pg/ml).

<p>Significant differences to baseline (repeated-measures ANOVA with Bonferroni posthoc comparisons) are indicated as follows: *p<0.05.</p><p>Free/bound epinephrine levels (pg/ml).</p

Free/bound norepinephrine levels (pg/ml).

<p>Significant differences to baseline (repeated-measures ANOVA with Bonferroni posthoc comparisons) are indicated as follows: ***p<0.001, **p<0.01, *p<0.05.</p><p>Free/bound norepinephrine levels (pg/ml).</p

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

<p>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) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106120#pone.0106120-Kroepfl2" target="_blank">[6]</a>. 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).</p