Abstract # 3124 The effect of acute and sustained beta2-adrenergic receptor stimulation on the function of Natural Killer cells

Abstract

Epinephrine is a neurotransmitter, which is produced by the adrenal glands and adrenergic neurons. It plays a crucial role during acute stress in the so-called fight-or-flight response. Additionally, epinephrine can act on the immune system. The number of lymphocytes in peripheral blood increases after exposure to epinephrine. More importantly, the outcome of cancer therapies and major surgery can be influenced by epinephrine-mediated effects on the immune system. Natural Killer (NK) cells are innate lymphoid cells that are involved in the control of viral infection and tumors. NK cells respond to epinephrine mainly through beta2-adrenergic receptor (beta2AR) signaling, which leads to increased cAMP levels in the cytoplasm. Our data show that beta2AR stimulation affects signal transduction of activating NK cell receptors. As a result, acute exposure of NK cells to epinephrine reduces NK cell cytotoxicity and production of interferon-gamma. More importantly, epinephrine blocks the affinity increase of the adhesion protein LFA-1, which can be induced through the stimulation of NK cell activating receptors. This suggests that beta2AR signaling interferes with LFA-1 mediated NK cell adhesion. Interestingly, chronic beta2AR exposure completely prevented the inhibitory effects of acute epinephrine stimulation on NK cell functions. Therefore, acute and chronic exposure to epinephrine can have very different effects on the function of immune cells, which may explain some effects of acute and chronic stress on the immune system.