Catecholamines increase lymphocyte beta 2-adrenergic receptors via a beta 2-adrenergic, spleen-dependent process

Abstract

We investigated the mechanisms underlying the increase in mononuclear leukocyte (MNL) beta 2-adrenergic receptor (AR) number and responsiveness after acute infusion of catecholamines. Infusion of isoproterenol and epinephrine, but not of norepinephrine, acutely increased MNL beta-AR density, and this was blocked by the beta 2-selective antagonist ICI 118,551 but not by the beta 1-selective antagonist bisoprolol, suggesting a beta 2-AR-mediated effect. Infusion of isoproterenol but not of norepinephrine also induced a lymphocytosis, with an increase in the number of circulating suppressor/cytolytic T (Ts/c)- and natural killer (NK)-cells but a decrease in helper T (Th)-cells, leading to a decreased Th-Ts/c-cell ratio. beta-AR density was higher in Ts/c-cells than in Th-cells. After isoproterenol infusion, beta-AR density was elevated in all lymphocyte subsets but not in monocytes or platelets, suggesting a lymphocyte-specific phenomenon. Infusion of isoproterenol in splenectomized patients did not alter lymphocyte subset composition and only slightly increased beta 2-AR density. In healthy subjects lymphocyte proliferation in response to various mitogens was attenuated after infusion of isoproterenol but not of norepinephrine; this effect was abolished in splenectomized patients. We conclude that the elevated MNL beta-AR density after acute exposure to beta-adrenergic agonists is caused by a release of lymphocyte subsets from the spleen into the circulation and/or by an exchange of lymphocyte subsets between the spleen and the circulation, whereby freshly released splenic lymphocytes appear to carry more beta-AR than those found in the circulation. This appears to impair immune responsiveness in a dual manner, by decreasing the Th-/Ts/c-cell ratio and by rendering lymphocytes more sensitive to the antiproliferative effects of catecholamines via a higher beta-AR density.

Sympathetic modulation of immunity: Relevance to disease

“…Human and murine T lymphocytes express β 2 -AR [54,55,[126][127][128][129][130][131][132][133][134][135][136][137][138][139][140]. T helper (Th)1 and Th2 cell clones generated from naïve cells differentially express β 2 -AR [141].…”

“…Based on radioligand binding and RT-PCR studies, B cells express a higher density of β-AR than CD4 + Th cells [54,126,129,131,133,[157][158][159]. These receptors are of the β 2 -AR subtype [54,129,131,160] and their stimulation also elevates intracellular concentrations of cAMP [127,131,[135][136][137]148,160].…”

Catecholamines—Crafty Weapons in the Inflammatory Arsenal of Immune/Inflammatory Cells or Opening Pandora’s Box?

“…It is well established now that immune/inflammatory cells express multiple receptors for catecholamines. Numerous types of adrenergic receptors have been identified on human and rodent PBMCs, macrophages, neutrophils, and lymphocytes (10,11,48,54,55). Dopamine receptor subtypes also have been described on these cells (50,56,57).…”

High levels of Gs alpha in platelets of euthymic patients with bipolar affective disorder

“…In particular, lymphocytes appear to be markedly affected by alterations in sympathetic nervous activity and circulating catecholamines. Indeed, it is noteworthy that acute activation of the sympathetic nervous system results in the release of "activated" lymphocyte subsets from the spleen into the circulation, and these lymphocyte subsets have properties (e.g., β-adrenoceptor responsiveness) that are markedly different from those of the "older," circulating lymphocytes (28)(29)(30). Since we did not measure the relative lymphocyte subpopulations in the present study, it remains a possibility that our failure to observe high levels of G s α in the patients with bipolar affective disorder is due (at least in part) to differences in lymphocyte subpopulations.…”