Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood via the β(2)-adrenergic receptor
| Autor: | Forrest L. Baker, Mitzi S. Laughlin, Richard J. Simpson, Rachel M. Graff, R. Azadan, Chad Dolan, Richard A. Bond, Chitra Hosing, Melissa M. Markofski, Hawley E. Kunz, Catherine M. Bollard, Nadia H. Agha |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Immunology Hemodynamics Antigens CD34 Placebo Article 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Double-Blind Method Nadolol Adrenergic beta-2 Receptor Antagonists Internal medicine Heart rate Granulocyte Colony-Stimulating Factor medicine Bisoprolol Humans Exercise Endocrine and Autonomic Systems business.industry Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells Hematopoietic Stem Cell Mobilization Haematopoiesis 030104 developmental biology Blood pressure Endocrinology Exercise intensity Peripheral Blood Stem Cells Female Receptors Adrenergic beta-2 business 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Popis: | 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 β2-adrenergic receptor (β2-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 (β1-AR antagonist); (ii) 80 mg nadolol (β1 + β2-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 β2-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 β2-AR signaling and hemodynamic shear stress. |
| Databáze: | OpenAIRE |
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