Mast Cell Serotonin Immunoregulatory Effects Impacting on Neuronal Function: Implications for Neurodegenerative and Psychiatric Disorders

Abstract

Mast cells (MCs) are derived from hemopoietic precursor cells, undergo their maturation in peripheral tissues, and play a significant role in both the innate and adaptive immune response. Cross-linking of the FcεRI on MCs initiates activation of several cytoplasmic protein tyrosine kinases which rapidly lead to phosphorylation and recruitment of adaptor molecules. These effects trigger the release of preformed mediators stored in the cytoplasmic granules, including histamine, serotonin and tryptase, as well as newly synthesized mediators, such as cytokines/chemokines, prostaglandins, leukotrienes, and growth factors. Serotonin (5-HT) is a bioactive monoamine, which has seven specific cell surface membrane bound receptors which are coupled to G-proteins, plays an important role in the central and peripheral nervous system, and is one of the key mediators in signaling between nervous and immune systems. Serotonin is not stored in all MC types but is implicated in MC adhesion, chemotaxis, tumorigenesis, and tissue regeneration through smooth muscle differentiation of stromal cells. Recent evidence indicates that serotonin has immunoregulatory actions that may be important in neuropsychiatric conditions. Chemokines, RANTES/CCL5, MCP-1/CCL2, and related molecules, constitute the C-C class of chemokine supergene family, play a role in regulating T helper-cell cytokine production and MC trafficking, and are involved in histamine and serotonin generation and MC functions. Pro-inflammatory cytokines such as interleukin-1-β and tumor necrosis factor which mediate MC response, are capable of activating p38 MAPK, and might increase serotonin generation through p38 MAPK activation. Here, we review the relationship between MCs and serotonin and its role in inflammatory diseases and neuroimmune interactions.

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

“…There are two possible explanations for this increase. First, the synthesis of serotonin (mast cells being its source in the eyelid) [29] can increase under the influence of substance P, a neuroinflammation factor whose content rises in the central nervous system in PD [30, 31]. Second, the elevated serotonin level in the eyelid can be rooted in its impaired metabolism; for example, resulting from a reduced activity of N-acetyltransferase, the rate-limiting enzyme for the conversion of serotonin to melatonin.…”

Alternative Anaphylactic Routes: The Potential Role of Macrophages

“…The role of serotonin in the anaphylactic process is still unknown, although recent reports have suggested that this metabolite is key in immune response regulation (23, 25) and, more specifically, in the regulation of macrophage polarization and inflammatory resolution (26, 27), allergy (28), and hypotension (29). Serotonin participation in the regulation of inflammation and immune response upon anaphylaxis will be further discussed.…”

Relation between mast cells concentration and serotonin expression in chagasic megacolon development

“…However, it has been suggested by others that mast cell mediators releases (prostaglandin D2, leukotriene B4, leukotriene C4, IL‐4, IL‐5, IL‐6 and IL‐13) may be modulated by a serotonin receptor mechanism. Undertaking a serotonin receptor‐mediated event, it can be considered that the effects of serotonin antagonism on mast cell activity are mainly mediated between the 5‐HT2A receptor subtype . It is plausible that reduced mast cell activity followed serotonin receptor antagonism might concurrently attenuate mast cell mediators releases and so indirectly reduce leukocyte‐endothelial interactions induced by mast cells.…”