Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis

Abstract

SUMMARYThe immune and the nervous systems are anatomically closely related and interact with each other by molecules common to both systems, such as cytokines and neurotransmitters. The purpose of this study was to investigate the participation of catecholamines in the neuroimmunological network. The ability of immune cells to produce catecholamines was examined by a highly sensitive capillary electrophoresis assay, which permits detection of easily oxidized catecholamines in the zeptomole (10 ÿ 21 ) range. In addition, the effects of catecholamines on in vitro proliferation, differentiation and apoptosis of lymphocytes were assessed. Mouse spleen cells and macrophages contained on average 7 2 10 ÿ 17 and 2 2 10 ÿ 17 mole dopamine per cell, respectively. In the former cell population also norepinephrine was found. Several mouse B-and T-cell hybridomas were also shown to contain endogenously produced dopamine in levels ranging from 7 2 10 ÿ 20 to 2 2 10 ÿ 18 mole dopamine per cell. In addition, one of the T-cell hybridomas proved to synthesize norepinephrine. The dopamine production of lymphocytes was blocked by the tyrosine hydroxylase inhibitor a -methyl-p-tyrosine, whereas incubation with the precursor L-DOPA increased the dopamine content. Incubation with L-DOPA, dopamine and norepinephrine dose-dependently suppressed mitogen induced proliferation and differentiation of mouse lymphocytes. Even short-time pretreatment of lymphocytes with L-DOPA and dopamine strongly suppressed lymphocyte proliferation and cytokine production. Incubation of lymphoid cells with L-DOPA, dopamine and norepinephrine dose-dependently induced apoptosis which, at least partly, explains the suppressive effects of catecholamines on lymphocyte function. Our results demonstrate that catecholamines: (i) are actively produced by lymphocytes and (ii) have the capacity to act as auto-and/or paracrine regulators of lymphocyte activity through induction of apoptosis.

Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity

“…Although some studies based on pharmacologic stimulation of DA receptors have suggested that DA could favor T cell activation by promoting surface expression of integrins and the secretion of TNF-a (12,14), it has also been suggested that DA is able to potently inhibit T cell activation, proliferation, and cytokine secretion (40)(41)(42). However, most of these studies use mixtures of T cell populations, high DA concentrations, and pharmacologic compounds of limited specificity.…”

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

“…Lymphocytes were described not only to contain intracellular levels of catecholamines, but these catecholamines were secreted, negatively regulating lymphocyte proliferation, differentiation, and apoptosis via an autocrine loop in mice and humans (13,14). Shortly thereafter, parallel experiments identified dopamine and norepinephrine in human PBMCs (15,16).…”

“…Following termination of their actions and cellular reuptake, catecholamines are oxidized intracellularly by the mitochondrion-associated MAO and the ubiquitous cytosolic COMT. During inactivation, catecholamines are degraded into various products including large quantities of reactive oxygen species and other cytotoxic oxidative metabolites, which are known to induce cellular apoptosis in mouse lymphocytes, human PBMCs, and PC12 cell lines (14,(64)(65)(66)(67). Newly synthesized intracellular catecholamines might not be released immediately but stored inside the cells, which may put cells in jeopardy of receptor-independent and oxidative stress-induced apoptosis (39).…”

Acute Effects of Dihydrocapsaicin and Capsaicin on the Distribution of White Blood Cells in Rats

“…1C). Catecholamine is known to exert a powerful impact on the immune system by downregulation of proliferation and differentiation of lymphocytes ( 27 ) and to induce apoptosis of lymphocytes ( 28 ). This decreased number of lymphocytes (lymphocytopenia) would be caused by apoptosis of lymphocytes induced by catecholamine.…”