β-Adrenergic receptor signaling mediates the preferential mobilization of differentiated subsets of CD8+ T-cells, NK-cells and non-classical monocytes in response to acute exercise in humans.

Rachel M Graff, Hawley E Kunz, Nadia H Agha, Forrest L Baker, Mitzi Laughlin, Austin B Bigley, Melissa M Markofski, Emily C LaVoy, Emmanuel Katsanis, Richard A Bond, Catherine M Bollard, Richard J Simpson

Journal: Brain, behavior, and immunity 2019;74():143-153

PMID: 30172948

Full Text on Elsevier Science View on PubMed

Abstract

Acute exercise preferentially mobilizes cytotoxic T-cells, NK-cells and non-classical monocytes to the bloodstream under the influence of hemodynamic forces and/or β-adrenergic receptor (β-AR) signaling. However, the relative contribution of these mechanisms to the redeployment of the most exercise-responsive cell types is largely unknown. We determined the lymphocyte and monocyte subtypes mobilized to blood during exercise via β-AR signaling whilst controlling for β-AR mediated reductions in hemodynamic forces. In a randomized, double blind, complete cross-over design, 14 healthy cyclists exercised for 30-minutes at +10% of blood lactate threshold after ingesting: (1) a placebo, (2) a β-preferential antagonist (10 mg bisoprolol), or (2) a non-preferential β + β-antagonist (80 mg nadolol) across three trials separated by >7-days. Bisoprolol was administered to reduce hemodynamic forces (heart rate and blood pressure) during exercise to levels comparable with nadolol but without blocking β-ARs. The mobilization of total NK-cells, terminally differentiated (CD57+) NK-cells, central memory, effector memory and CD45RA+ effector memory CD8+ T-cells; non-classical monocytes; and γδ T-cells were significantly blunted or abrogated under nadolol compared to both bisoprolol and placebo, indicating that the exercise-induced mobilization of these cell types to the blood is largely influenced by β-AR signaling. Nadolol failed to inhibit the mobilization of classical monocytes, CD4+ T-cells (and their subsets) or naïve CD8+ T-cells, indicating that these cell types are mobilized with exercise independently of the β-AR. We conclude that the preferential mobilization of NK-cells, non-classical monocytes and differentiated subsets of CD8+ T-cells with exercise is largely dependent on catecholamine signaling through the β-AR. These findings provide mechanistic insights by which distinct lymphocyte and monocyte subtypes are preferentially mobilized to protect the host from anticipated injury or infection in response to an acute stress response.

Address: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, TX, USA.; Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, TX, USA; Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA; Department of Pediatrics, University of Arizona, Tucson, AZ, USA.; Department of Pediatrics, University of Arizona, Tucson, AZ, USA; Department of Immunobiology, University of Arizona, Tucson, AZ, USA.; The University of Houston, College of Pharmacy, Science and Engineering Research Center, 4849 Calhoun Blvd, Houston, TX, USA.; Center for Cancer and Immunology Research, Children's Research Institute, Children's National Health System and The George Washington University, Washington D.C., USA.; Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, TX, USA; Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA; Department of Pediatrics, University of Arizona, Tucson, AZ, USA; Department of Immunobiology, University of Arizona, Tucson, AZ, USA; Department of Behavioral Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: [email protected].

DOI: 10.1016/j.bbi.2018.08.017

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MeSH Terms: Adult, Bisoprolol, CD8-Positive T-Lymphocytes, Catecholamines, Cross-Over Studies, Double-Blind Method, Exercise, Female, Healthy Volunteers, Humans, Killer Cells, Natural, Lymphocyte Activation, Male, Monocytes, Nadolol, Receptors, Adrenergic, beta-2, Signal Transduction