Expression of Tyrosine Hydroxylase in Lymphocytes and Effect of Endogenous Catecholamines on Lymphocyte Function

Abstract

Objectives: To comprehend the changes and significance of the endogenous catecholamines in the immune system, we explored the synthesis of catecholamines by lymphocytes in various lymphoid organs and in different activated states, and the effect of the endogenous catecholamines synthesized by lymphocytes on the function of the lymphocytes themselves. Methods: Immunohistochemistry for lymphoid organs (mesenteric lymph nodes, spleen and thymus) and lymphocytes was used to observe their expression of tyrosine hydroxylase (TH), an initial rate-limiting enzyme of the catecholamine synthesis. The contents of catecholamines, including norepinephrine (NE), dopamine (DA) and epinephrine (E), in lymphocytes were tested by means of high-performance liquid chromatography with electrochemical detection. Western blot was used to examine the character and relative quantity of TH-stained protein in lymphocytes, lymph nodes and adrenal medullary tissue. The effect of α-methyl-p-tyrosine (α-MT), an inhibitor of TH activity, on concanavalin A (Con A)-induced interleukin-2 (IL-2) production was determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Results: TH-positive cells were found in the three examined lymphoid organs, but the lymph nodes had the highest and the thymus had the lowest density. Both TH expression and the contents of NE, DA and E in the Con A-activated lymphocytes were markedly increased in comparison with those in the nonactivated lymphocytes. A band with TH immunoreactivity was seen in the extracts from either Con A-activated lymphocytes or nonactivated cells and the molecular weight of the protein was 59.4 ± 0.3 kD. However, the relative quantity of the protein was notably higher in the activated lymphocytes than in the nonactivated cells. As a positive control, a similar band of TH immunoreactivity in the adrenal medullary tissue was also obtained. α-MT at the doses of 10^–11, 10^–10 and 10^–9 M was found to significantly facilitate the Con A-induced IL-2 production. Conclusions: These results suggest that lymphocytes can synthesize catecholamines and their synthesis levels may increase in the activated state, and that endogenous catecholamines synthesized by the lymphocytes can regulate the function of the lymphocytes themselves.

Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue

“…1A). Other sources of NE could be found in the SVF of PVAT, such as macrophages (11), lymphocytes (58), and neurons. The catecholamines present in PVAT are releasable by tyramine and support contraction in the rat superior mesenteric artery independent of sympathetic innervation (5).…”

Ontogeny of Intrinsic Innervation in the Human Thymus and Spleen

“…Recent data suggest that lymphocytes may express TH and can thus synthesize catecholamines, especially when activated (Qiu et al 2004). According to Kranz et al (1997), TH-specific immunoreactivity has been identified in thymic cortical epithelial cells of children, whereas only a few TH-positive cells have been found in the medulla.…”

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

“…Recently, rat phagocytes were found to contain mRNA for both TH and DBH, which clearly were inducible by cell contact with bacterial lipopolysaccharide (LPS) (11). In parallel, rat lymphocytes (22,23) and human PBMCs (24) contain inducible mRNA for these catecholamine-generating enzymes, upregulation of which results in increased levels of dopamine, norepinephrine, and epinephrine when rat lymphocytes were stimulated (22). In contrast, pharmacological inhibition of TH and DBH in rat and human lymphocytes decreased intracellular catecholamine levels in a dose-dependent manner (22,25).…”

“…However, it was not until the mid 1990s that it was reported that lymphocyte-derived catecholamines modulate lymphocyte functions in an autocrine and paracrine manner, providing these cells with a potent tool to fine tune their actions and crosstalk with nearby cells (13). Because the expression of TH and DBH mRNA has been found to be inducible by various stimuli when compared with non-stimulated lymphocytes, it seems likely that the catecholamine synthesis in lymphocytes and phagocytes depends on the functional state of these cells, and that there are diverse cell triggers (11,19,22,23). These auto-regulatory interactions between endogenous catecholamines and immune/ inflammatory cells can alter a wide array of cell functions, in part through adrenoceptors or dopaminergic receptors expressed on these cells (10,11,47,48) (see below).…”