Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin

Boehme, Stefen A.; Lio, Francisco M.; Sikora, Lyudmila; Pandit, Terlika S.; Lavrador, Karine; Rao, Savita P.; Sriramarao, P.

doi:10.4049/jimmunol.173.6.3599

Cited by 101 publications

(87 citation statements)

References 18 publications

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“…Serotonin directly modulates functions of several other immune cells, but unlike in the case of dendritic cells, mast cells, and eosinophils, serotonin did not act as a chemoattractant to induce in vitro migration of neutrophils. 7,[41][42][43][44] In vitro plateletneutrophil rosetting was also independent of the platelet serotonin content, indicating that serotonin does not influence platelet P-selectin expression and platelet-neutrophil interactions. It is more probable that serotonin enhances neutrophil extravasation by regulating endothelial selectin expression, because serotonin induces WPB exocytosis in cultured endothelial cells 10,11 and injection of serotonin enhanced leukocyte rolling in the Tph1 Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 96%

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

Duerschmied

Suidan

Demers

et al. 2013

Blood

274

231

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Key Points• During inflammation, serotonin released by platelets activates vessel wall promoting leukocyte adhesion and recruitment.• Absence of platelet serotonin improves survival after lipopolysaccharide-induced endotoxic shock.The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1-deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1 ؊/؊ mice. The velocity of rolling leukocytes was higher in Tph1 ؊/؊ mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1 ؊/؊ mice. Diminished rolling in Tph1 ؊/؊ mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1 ؊/؊ mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1 ؊/؊ mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. (Blood. 2013;121(6):1008-1015) IntroductionPlatelets store serotonin in their dense granules at millimolar concentration and secrete it when they become activated. 1,2 This requires a complex mechanism of uptake, storage, and targeted release that is similar to that in neurons, with the exception that platelets are not stationary but circulate in high numbers throughout the vasculature. Platelets do not synthesize serotonin but incorporate and store serotonin that is synthesized in duodenal enterochromaffin cells and secreted into blood. Several different effects of non-neuronal serotonin have been unraveled in the past, including prohemostatic (on platelets and vascular smooth muscle cells), 3,4 mitogenic (on hepatocytes and pulmonary smooth muscle cells), 5,6 and immunomodulatory (on lymphocytes, monocytes, and smooth muscle cells) 7-9 functions. In vitro studies have shown that serotonin also activates the release of Weibel-Palade bodies (WPBs) from endothelial cells, which would promote leukocyte rolling via the WPB constituent P-selectin. 10,11 However, it is not clear whether serotonin influences neutrophil-endothelial interactions, a central step in early innate immune responses.We chose 2 approaches to study serotonin effects on leukocyte rolling and recruitment: genetic defi...

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Section: Discussionmentioning

confidence: 96%

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

Duerschmied

Suidan

Demers

et al. 2013

Blood

274

231

View full text Add to dashboard Cite

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“…Time-lapse imaging of interneurons in embryonic slices revealed that the application of 5-HT decreased Evidence for a role of 5-HT in cell migration has been demonstrated in nonneuronal cells such as eosinophils in the immune system, 31 pulmonary artery cells, 32 aortic endothelial cells 33 and mesenchymal cells derived from the cranial neural crest. 34 Interestingly in the nematode Caenorhabditis elegans, long-distance neuronal migration was shown to be under the regulation of 5-HT.…”

Section: Discussionmentioning

confidence: 99%

Excess of serotonin affects embryonic interneuron migration through activation of the serotonin receptor 6

et al. 2008

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The discovery that a common polymorphism (5-HTTLPR, short variant) in the human serotonin transporter gene (SLC6A4) can influence personality traits and increase the risk for depression in adulthood has led to the hypothesis that a relative increase in the extracellular levels of serotonin (5-HT) during development could be critical for the establishment of brain circuits. Consistent with this idea, a large body of data demonstrate that 5-HT is a strong neurodevelopmental signal that can modulate a wide variety of cellular processes. In humans, serotonergic fibers appear in the developing cortex as early as the 10th gestational week, a period of intense neuronal migration. In this study we hypothesized that an excess of 5-HT could affect embryonic cortical interneuron migration. Using time-lapse videometry to monitor the migration of interneurons in embryonic mouse cortical slices, we discovered that the application of 5-HT decreased interneuron migration in a reversible and dose-dependent manner. We next found that 5-HT6 receptors were expressed in cortical interneurons and that 5-HT6 receptor activation decreased interneuron migration, whereas 5-HT6 receptor blockade prevented the migratory effects induced by 5-HT. Finally, we observed that interneurons were abnormally distributed in the cerebral cortex of serotonin transporter gene (Slc6a4) knockout mice that have high levels of extracellular 5-HT. These results shed new light on the neurodevelopmental alterations caused by an excess of 5-HT during the embryonic period and contribute to a better understanding of the cellular processes that could be modulated by genetically controlled differences in human 5-HT homeostasis.

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“…In most phyla, 5-HT triggers motility of various cell types including vertebrate lymphocytes (chick, fish, rodent [185,186]) and microglia towards the CNS [170]. In the mammalian cortex, a role for 5-HT in regulating the migration of cortical neurons has recently emerged.…”

Section: Serotonin and Neuronal Migrationmentioning

confidence: 99%

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

Vitalis¹,

Verney²

2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

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The mammalian cerebral cortex is critical for sensory and motor integrations and, for higher-order cognitive functions. The construction of mammalian cortical circuits involves the coordinated interplay between cellular processes such as proliferation, migration and differentiation of neural and glial cell subtypes followed by accurate connectivity evolving in complexity in primates. Alteration in cortical development may induce the emergence of various pathological traits and behaviours. Among the large array of factors that regulate the assembly of cortical circuits, serotonin (5-HT) plays important role as a developmental signal that impacts on a broad diversity of cellular processes. 5-HT plays distinct roles during specific sensitive periods and is produced from various sources depending on the perinatal stage. Its roles are mediated by more than fourteen 5-HT receptors that are all G-protein coupled receptors except the ionotropic 5-HT type 3A receptor (5-HT 3A ) mediating rapid neuronal activation. Importantly, 5-HT metabolism and signalling are influenced by numerous epigenetic and genetic factors, including nutrition and gut microbiota, perinatal stress, infection and inflammation. In this review, we will recapitulate some evidences showing that dysregulation of 5-HT homeostasis and 5-HT 3A signalling impairs distinct steps of cortical circuit formation leading to the predisposition of the onset of various psychiatric diseases.

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Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin

Cited by 101 publications

References 18 publications

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

Excess of serotonin affects embryonic interneuron migration through activation of the serotonin receptor 6

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

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