Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses.

Autor:	Devi S; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, Victoria, 3000, Australia., Alexandre YO; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia., Loi JK; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia., Gillis R; Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052 Australia., Ghazanfari N; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia., Creed SJ; Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052 Australia., Holz LE; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, Victoria, 3000, Australia., Shackleford D; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052 Australia., Mackay LK; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia., Heath WR; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, Victoria, 3000, Australia., Sloan EK; Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052 Australia; Division of Surgery, Peter MacCallum Cancer Center, Victoria, 3000, Australia., Mueller SN; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, Victoria, 3000, Australia. Electronic address: smue@unimelb.edu.au.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2021 Jun 08; Vol. 54 (6), pp. 1219-1230.e7. Date of Electronic Publication: 2021 Apr 28.
DOI:	10.1016/j.immuni.2021.03.025
Abstrakt:	The sympathetic nervous system (SNS) controls various physiological functions via the neurotransmitter noradrenaline. Activation of the SNS in response to psychological or physical stress is frequently associated with weakened immunity. Here, we investigated how adrenoceptor signaling influences leukocyte behavior. Intravital two-photon imaging after injection of noradrenaline revealed transient inhibition of CD8 + and CD4 + T cell locomotion in tissues. Expression of β-adrenergic receptor in hematopoietic cells was not required for NA-mediated inhibition of motility. Rather, chemogenetic activation of the SNS or treatment with adrenergic receptor agonists induced vasoconstriction and decreased local blood flow, resulting in abrupt hypoxia that triggered rapid calcium signaling in leukocytes and halted cell motility. Oxygen supplementation reversed these effects. Treatment with adrenergic receptor agonists impaired T cell responses induced in response to viral and parasitic infections, as well as anti-tumor responses. Thus, stimulation of the SNS impairs leukocyte mobility, providing a mechanistic understanding of the link between adrenergic receptors and compromised immunity. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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