Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes.

Abstract

We studied the catecholamine (CA) content in peripheral human lymphocytes and the ability of these cells to synthesize CA in vitro. CA were separated by high performance liquid chromatography (HPLC) and determined in the supernatant by electrochemical detection as well as being determined after ultrasonic cell disruption in mononuclear leukocytes, adherent cells (monocytes/macrophages), total lymphocytes, and B- and T-cell enriched fractions. T lymphocytes contained L-Dopa and norepinephrine (NE), whereas B lymphocytes contained only L-Dopa. Lymphocytes seem to be able to synthesize NE from both L-tyrosine and L-Dopa added to the incubation medium in concentrations similar to the peripheral venous plasma (i.e. 5 x 10(-5) m and 10(-8) m, respectively). The addition of D-Dopa did not increase intracellular NE. alpha-methyl-p-L-tyrosine, benserazide, disulfiram, and fusaric acid (which are inhibitors of the enzymatic pathway) all decreased the synthesis of NE. After the addition of [3H]-L-Dopa (10(-8) m and 10(-7) m) to the incubation medium, [3H]-NE and [3H]-dopamine appeared. By increasing the concentration of L-Dopa in the medium (< 10(-6) m), CA were detected in the supernatant as well. These data show that peripheral human T lymphocytes contain and are able to synthesize CA from normal precursors in physiologic concentrations, i.e. a CA synthetic pathway is shown in nonneural cells. These data seem to support the hypothesis of autocrine and paracrine loops in the regulation of lymphocyte activity in lymphocytes taken from human cerebrospinal fluid (as suggested by other authors).

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

“…Early sepsis is characterized by high levels of circulating catecholamines [20,60,61] that derive from the autonomous nervous system, the gut [62], lymphocytes [63,64] macrophages [65] and neutrophils [66,67]. A major mechanism of sepsis-induced cardiac dysfunction is the attenuation of the adrenergic response at the cardiomyocyte level due to down-regulation of β-adrenergic receptors [68,69] and depression of post-receptor signaling pathways [70][71][72][73].…”

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

“…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). Blockade of the conversion of dopamine to norepinephrine (by DBH-inhibition) increased intracellular levels of dopamine and other norepinephrine precursor molecules in human PBMCs (25).…”

“…In contrast, pharmacological inhibition of TH and DBH in rat and human lymphocytes decreased intracellular catecholamine levels in a dose-dependent manner (22,25). Blockade of the conversion of dopamine to norepinephrine (by DBH-inhibition) increased intracellular levels of dopamine and other norepinephrine precursor molecules in human PBMCs (25). Therefore, it is not surprising that the addition of tyrosine and L-DOPA to lymphocyte cultures increases catecholamine levels in these cells in a dose-dependent manner (25 were detected in these cells, suggesting an active uptake mechanism of catecholamine-precursor molecules from the extracellular fluids into human PBMCs (25).…”

“…Blockade of the conversion of dopamine to norepinephrine (by DBH-inhibition) increased intracellular levels of dopamine and other norepinephrine precursor molecules in human PBMCs (25). Therefore, it is not surprising that the addition of tyrosine and L-DOPA to lymphocyte cultures increases catecholamine levels in these cells in a dose-dependent manner (25 were detected in these cells, suggesting an active uptake mechanism of catecholamine-precursor molecules from the extracellular fluids into human PBMCs (25). Interestingly, these metabolic events are highly selective, because, in contrast to L-dopa, D-dopa failed to alter catecholamine synthesis in human PBMCs (25).…”

“…Therefore, it is not surprising that the addition of tyrosine and L-DOPA to lymphocyte cultures increases catecholamine levels in these cells in a dose-dependent manner (25 were detected in these cells, suggesting an active uptake mechanism of catecholamine-precursor molecules from the extracellular fluids into human PBMCs (25). Interestingly, these metabolic events are highly selective, because, in contrast to L-dopa, D-dopa failed to alter catecholamine synthesis in human PBMCs (25). However, human PBMC presents a highly heterogenous group of cells (lymphocytes, monocytes, etc.…”