Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, TX 77204, USA.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Brain Behav Immun. 2018 Feb;68:66-75. doi: 10.1016/j.bbi.2017.10.001. Epub 2017 Oct 7.
Acute dynamic exercise mobilizes CD34+ hematopoietic stem cells (HSCs) to the bloodstream, potentially serving as an economical adjuvant to boost the collection of HSCs from stem cell transplant donors. The mechanisms responsible for HSC mobilization with exercise are unknown but are likely due to hemodynamic perturbations, endogenous granulocyte-colony stimulating factor (G-CSF), and/or β-adrenergic receptor (β-AR) signaling. We characterized the temporal response of HSC mobilization and plasma G-CSF following exercise, and determined the impact of in vivo β-AR blockade on the exercise-induced mobilization of HSCs. Healthy runners (n = 15) completed, in balanced order, two single bouts of steady state treadmill running exercise at moderate (lasting 90-min) or vigorous (lasting 30-min) intensity. A separate cohort of healthy cyclists (n = 12) completed three 30-min cycling ergometer trials at vigorous intensity after ingesting: (i) 10 mg bisoprolol (β-AR antagonist); (ii) 80 mg nadolol (β + β-AR antagonist); or (iii) placebo, in balanced order with a double-blind design. Blood samples collected before, during (runners only), immediately after, and at several points during exercise recovery were used to determine circulating G-CSF levels (runners only) and enumerate CD34+ HSCs by flow cytometry (runners and cyclists). Steady state vigorous but not moderate intensity exercise mobilized HSCs, increasing the total blood CD34+ count by ∼4.15 ± 1.62 Δcells/µl (+202 ± 92%) compared to resting conditions. Plasma G-CSF increased in response to moderate but not vigorous exercise. Relative to placebo, nadolol and bisoprolol lowered exercising heart rate and blood pressure to comparable levels. The number of CD34+ HSCs increased with exercise after the placebo and bisoprolol trials, but not the nadolol trial, suggesting β-AR signaling mediated the mobilization of CD34+ cells [Placebo: 2.10 ± 1.16 (207 ± 69.2%), Bisoprolol 1.66 ± 0.79 (+163 ± 29%), Nadolol: 0.68 ± 0.54 (+143 ± 36%) Δcells/µL]. We conclude that the mobilization of CD34+ HSCs with exercise is not dependent on circulating G-CSF and is likely due to the combined actions of β-AR signaling and hemodynamic shear stress.
急性动力性运动将 CD34+造血干细胞 (HSCs) 动员到血液中，可能作为一种经济的辅助手段，从干细胞移植供体中增加 HSCs 的采集。运动时 HSC 动员的机制尚不清楚，但可能与血液动力学改变、内源性粒细胞集落刺激因子 (G-CSF) 和/或β-肾上腺素能受体 (β-AR) 信号有关。我们描述了运动后 HSC 动员和血浆 G-CSF 的时间反应，并确定了体内β-AR 阻断对运动诱导 HSC 动员的影响。健康跑步者（n=15）以平衡的顺序完成两次稳态跑步机运动，强度适中（持续 90 分钟）或剧烈（持续 30 分钟）。另一组健康骑自行车者（n=12）在摄入以下三种 30 分钟剧烈强度的自行车测力计试验后完成：（i）10mg 比索洛尔（β-AR 拮抗剂）；（ii）80mg 纳多洛尔（β+β-AR 拮抗剂）；或（iii）安慰剂，采用双盲设计以平衡的顺序。在运动前、运动中（仅跑步者）、运动后立即以及运动恢复的几个时间点采集血液样本，用于确定循环 G-CSF 水平（仅跑步者）和通过流式细胞术计数 CD34+HSCs（跑步者和骑自行车者）。稳态剧烈但不是中等强度的运动动员了 HSCs，使总血液 CD34+计数增加了约 4.15±1.62Δ细胞/μl（增加 202±92%），与静息状态相比。血浆 G-CSF 对中等强度运动有反应，但对剧烈运动没有反应。与安慰剂相比，纳多洛尔和比索洛尔将运动时的心率和血压降低到类似水平。与安慰剂和比索洛尔试验后相比，运动后 CD34+HSCs 的数量增加，但纳多洛尔试验后没有增加，这表明β-AR 信号介导了 CD34+细胞的动员[安慰剂：2.10±1.16（207±69.2%），比索洛尔 1.66±0.79（163±29%），纳多洛尔：0.68±0.54（143±36%）Δ细胞/μL]。我们得出结论，运动时 CD34+HSCs 的动员不依赖于循环 G-CSF，可能是β-AR 信号和血液动力学切应力共同作用的结果。
