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

Abstract

It is well established that catecholamines (CAs), which regulate immune and inflammatory responses, derive from the adrenal medulla and from presynaptic neurons. Recent studies reveal that T cells also can synthesize and release catecholamines which then can regulate T cell function. We have shown recently that macrophages and neutrophils, when stimulated, can generate and release catecholamines de novo which, then, in an autocrine/paracrine manner, regulate mediator release from these phagocytes via engagement of adrenergic receptors. Moreover, regulation of catecholamine-generating enzymes as well as degrading enzymes clearly alter the inflammatory response of phagocytes, such as the release of proinflammatory mediators. Accordingly, it appears that phagocytic cells and lymphocytes may represent a major, newly recognized source of catecholamines that regulate inflammatory responses.

Enhanced Phosphorylation of MAPKs by NE Promotes TNF-α Production by Macrophage Through α Adrenergic Receptor

“…NE apparently displayed an α-receptor-like effect as macrophages were activated by LPS. This is likely due to the fact that in LPS-activated macrophages, the effect of α receptor outweighed that of β receptor; consequently, NE displayed a proinflammatory role [7,20]. Furthermore, it was reported that α1 receptor on LPS-activated macrophage correlated with G q closely, which resulted in the release of proinflammatory cytokines from macrophages [25].…”

“…Some researchers reported that adrenergic receptors were diversely expressed in various tissue-fixed macrophages [7]. For example, β and α2 adrenergic receptors were all expressed in mouse peritoneal macrophages [19][20][21]. It was also reported that expression of adrenergic receptors on macrophages could be regulated by many kinds of factors [22].…”

Neuroimmunology

“…Upon release from the nerve terminal, NE is metabolized by catechol-O-methyltransferase and/or monoamine oxidase, taken back up into the nerve terminal, lost by diffusion, or bound to a receptor on a target cell. A recent report shows that, in addition to sympathetic nerve terminals, phagocytes also release NE and express the enzymes for NE synthesis and degradation (Flierl et al, 2007(Flierl et al, , 2008, providing another mechanism by which NE could be released within the microenvironment of an ongoing immune response to modulate immune cell activity.…”

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

“…The sympathetic nervous system (SNS) innervates the adrenal gland, resulting in the secretion of catecholamines (CA) into the systemic circulation; in turn, CA up-regulate the transcription of proinflammatory cytokines (Nance and Sanders, 2007). CA can modulate the proliferation and differentiation of immune cells, as well as cytokine production (Flierl et al, 2008;Peng et al, 2004;Torres et al, 2005). In this context, the sympathetic nervous system is also able to modulate the induction of Treg cells (Bhowmick et al, 2009) via a TGF-β-dependent mechanism, thus acting as a bridge between the immune and the nervous systems.…”