TY - JOUR
T1 - Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood via the β 2 -adrenergic receptor
AU - Agha, Nadia H.
AU - Baker, Forrest L.
AU - Kunz, Hawley E.
AU - Graff, Rachel
AU - Azadan, Rod
AU - Dolan, Chad
AU - Laughlin, Mitzi S.
AU - Hosing, Chitra
AU - Markofski, Melissa M.
AU - Bond, Richard A.
AU - Bollard, Catherine M.
AU - Simpson, Richard J.
N1 - Funding Information:
This work was supported by NASA Grants NNJ10ZSA003N , NNJ14ZSA001N-FLAGSHIP and NNJ14ZSA001N-MIXEDTOPICS to R.J. Simpson, NIH Grant R21 CA197527-01A1 to R.J. Simpson, ACSM NASA Foundational Research Grant to N. Agha, and NIH grant P01 CA148600-01A1 to C.M. Bollard.
Publisher Copyright:
© 2017
PY - 2018/2
Y1 - 2018/2
N2 - 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 2 -adrenergic receptor (β 2 -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 1 -AR antagonist); (ii) 80 mg nadolol (β 1 + β 2 -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 2 -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 2 -AR signaling and hemodynamic shear stress.
AB - 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 2 -adrenergic receptor (β 2 -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 1 -AR antagonist); (ii) 80 mg nadolol (β 1 + β 2 -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 2 -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 2 -AR signaling and hemodynamic shear stress.
KW - Bisoprolol
KW - CD133
KW - Exercise immunology
KW - Exercise intensity
KW - Granulocyte colony stimulating factor (G-CSF)
KW - Hematopoietic stem cell transplantation
KW - Nadolol
KW - Progenitor cells
KW - β-AR blockade
UR - http://www.scopus.com/inward/record.url?scp=85031662462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031662462&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2017.10.001
DO - 10.1016/j.bbi.2017.10.001
M3 - Article
C2 - 29017969
AN - SCOPUS:85031662462
SN - 0889-1591
VL - 68
SP - 66
EP - 75
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -