Regulation of Natural Killer Cell Functions by Catecholamines
Final Report Abstract
Receptors for Catecholamines are preferentially expressed by innate lymphocytes such as Natural Killer (NK) cells. In this project we studied the effect of catecholamines, especially epinephrine and dopamine, on the function of human NK cells. Epinephrine stimulation inhibited early NK cell signaling events and blocked the function of the integrin LFA-1. This reduced the adhesion of NK cells to ICAM-1, explaining how NK cells are mobilized into the peripheral blood upon epinephrine release during acute stress or exercise. Additionally, epinephrine stimulation transiently reduced NK cell degranulation, serial killing, cytokine production, and affected metabolic changes upon NK cell activation via the cAMP-PKA pathway. Repeated exposure to β2AR agonists resulted in the desensitization of the β2AR via a PKA feedback loopinitiated G-protein switch. Therefore, acute epinephrine stimulation of chronically β2AR stimulated NK cells no longer resulted in inhibited signaling and reduced LFA-1 activity. Sustained stimulation by long-acting β2 agonists (LABA) not only inhibited NK cell functions but also resulted in desensitization of the β2AR. However, peripheral NK cells from LABA-treated asthma patients still reacted unchanged to epinephrine stimulation, demonstrating that local LABA administration does not result in detectable systemic effects on NK cells. Upon stimulation of dopaminergic receptors (DR) on NK cells we found an inhibitory effect of D1-like DR, but no effects of D2-like DR. Metabolic analysis did not reveal any effect of DR stimulation, and cAMP pathway was also not altered, thus suggesting that non-canonical pathways are probably involved in the dopaminergic effect on NK cells.
Publications
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Regulation of natural killer cell activity by glucocorticoids, serotonin, dopamine, and epinephrine. Cellular & Molecular Immunology, 17(7), 705-711.
Capellino, Silvia; Claus, Maren & Watzl, Carsten
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Catecholamines and Immunomodulation. Masterclass in Neuroendocrinology, 105-133. Springer International Publishing.
Claus, Maren & Capellino, Silvia
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Chronic stimulation desensitizes β2‐adrenergic receptor responses in natural killer cells. European Journal of Immunology, 54(12).
Jürgens, Martin; Claus, Maren; Wingert, Sabine; Niemann, Jens Alexander; Picard, Lea Katharina; Hennes, Elisabeth; Haasler, Ina; Hellwig, Birte; Overbeck, Nina; Reinders, Jörg; Rahnenführer, Jörg; Schedel, Michaela; Capellino, Silvia & Watzl, Carsten
