Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice

Amireault, Pascal; Hatia, Sarah; Bayard, Elisa; Bernex, Florence; Collet, Corinne; Crinon, Jacques; Launay, Jean‐Marie; Hermine, Olivier; Schneider, Elke; Mallet, Jacques; Dy, Michel; Côté, Francine

doi:10.1073/pnas.1103964108

Cited by 67 publications

(65 citation statements)

References 45 publications

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“…78 We revealed a pivotal role for 5-HT in erythropoiesis and red blood cell survival using the Tph1−/− KO mouse. 79 Our data established that 5-HT regulates in vivo erythropoiesis as 5-HT−deficient animals present a phenotype of macrocytic anemia due to an ineffective erythropoiesis. In the bone marrow, absence of 5-HT down-regulates the rate of red blood cell production since erythroid precursors progression toward terminal differentiation is hampered.…”

Section: ■ Serotonin and Red Blood Cell Production And Survivalmentioning

confidence: 82%

“…In vitro experiments with isolated Tph1−/− erythroid precursors showed they have a decreased proliferative capacity, that is restored by addition of 5-HT, suggesting they possess the capacity to synthesize 5-HT. 79 Further evidence to support a direct role for 5-HT in erythroid cells came from binding experiments demonstrating the presence of 5-HT 2A and 5-HT 2B receptors and SERT on erythroid precursors. On the basis of our data, although the definitive presence of Tph1 has yet to be proven, we propose that a local paracrine/autocrine serotonergic network exists in erythroid cells.…”

Section: ■ Serotonin and Red Blood Cell Production And Survivalmentioning

confidence: 99%

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Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Amireault

Sibon

Côté

2012

ACS Chem. Neurosci.

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138

113

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Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

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Section: ■ Serotonin and Red Blood Cell Production And Survivalmentioning

confidence: 82%

Section: ■ Serotonin and Red Blood Cell Production And Survivalmentioning

confidence: 99%

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Amireault

Sibon

Côté

2012

ACS Chem. Neurosci.

Self Cite

138

113

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“…20 Recently, the absence of 5-HT was shown to reduce erythroid precursors in BM via 5-HT 2A and 5-HT 2B Rs because a 5-HT 2 agonist, PNU 22394, produced the same proliferative effect on erythroid precursors as observed with 5-HT. 28 At early stages of megakaryocytopoiesis, 5-HT regulates proliferation and survival by antiapoptotic effects on megakaryoblastic cells. 40 On megakaryocytic cell line HEL, pretreatment with 5-HT protected subsequent nitric oxide-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…20,28 We have assessed the effect of 5-HT 2B R blockade using the selective antagonist, RS-127445, during the differentiation of total BM cell cultures from mice. When mice BM was used in methylcellulose colony-forming assay, we observed a significant reduction in both CFU-GEMM/CFU-GM and CFU-E/BFU-E colonies with the 5-HT 2B R antagonist ( Figure 4A).…”

Section: Alterations Of Bm Differentiation After 5-ht 2b R Inhibitionmentioning

confidence: 99%

Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension

Launay

Hervé

Crinon

et al. 2012

Blood

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Pulmonary arterial hypertension (PAH) is IntroductionPulmonary arterial hypertension (PAH) is a rare but fatal disease, often of unknown origin, characterized by progressive increase in pulmonary vascular resistance and remodeling associated with vasoconstriction. 1 PAH is histologically characterized by a neomuscularization of small pulmonary arteries with intimal thickening, medial hypertrophy, adventitial proliferation, and abnormal extracellular matrix deposition. The progression of vascular remodeling results in vascular lumen narrowing, increased pulmonary artery resistance, hypoxia, and right heart hypertrophy, although the molecular pathways initiating this remodeling are not clearly established.On the one hand, stem cells, resident or not, may give rise to a significant proportion of differentiating/proliferating smooth muscle cells (SMCs) that contribute to intimal hyperplasia in lung vascular remodeling. 2 Moreover, genetic ablation of the transmembrane tyrosine kinase receptor for stem cell factor/c-kit pathway results in a marked reduction in intimal hyperplasia in animal models of vascular injury; conversely, wild-type (WT) bone marrow (BM) reconstitution in c-kit mutant mice led to intimal hyperplasia comparable with WT animals. 3 Pharmacologic antagonism of the c-kit pathway with STI-571 (imatinib mesylate; Gleevec) also results in a marked reduction in hyperplasia. 3 Mobilization of c-kit expressing cells from BM to blood circulation is a physiologic response to hypoxia. Increasing evidence supports the idea that these progenitor cells of BM origin may also contribute to vascular wall remodeling that is characteristic of PAH. [4][5][6][7][8] However, it is unclear, whether this entry of progenitors represents a protective or a worsening process in the development of PAH. 9 Other observations have also identified an association between PAH and BMrelated hematologic disorders 10 : in proliferative disorders of the hematopoietic stem cells such as myeloproliferative cancers, there is an unexplained high incidence of PAH. PAH is now a recognized complication of BM transplantation for leukemia, 11 chronic myeloproliferative disorders, 12 or in the treatment of malignant infantile osteopetrosis. 13 On the other hand, serotonin (5-hydroxytryptamine ) is associated with the pathogenesis of PAH. 14 Therapeutic drugs with PAH as a side effect, such as the amphetamine derivative and anorexigen dexfenfluramine, are potent 5-HT releasers acting at 5-HT transporter (SERT) and/or agonists at 5-HT receptors (5-HTRs). 15 An over-expression of 5-HT 2B Rs is observed in PAH. 16 Blockade of 5-HT 2B Rs using independent approaches, either genetic (5-HT 2B R knock-out mice; 5-HT 2B Ϫ/Ϫ ) or pharmacologic (5-HT 2B antagonist RS-12744) inactivation, completely prevented the development of hypoxia-induced pulmonary hypertension in mice. 16 By using the monocrotaline (MCT)-induced pulmonary hypertension rat model, recent studies confirmed that other 5-HT 2B antagonists (terguride, PRX-08066, or C-122) significantly reduc...

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“…Together, these differences make a direct comparison difficult. More recently, an intriguing study demonstrated the importance of 5-HT in effective erythropoiesis, where the absence of 5-HT decreased differentiation of erythroid precursors and increased phagocytosis of erythrocytes (46). Like apoptotic cells, aging erythrocytes externalize phosphatidylserine on their outer membrane allowing them to be recognized and removed by phagocytes (47)(48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine Signaling Via the Serotonin Transporter Regulates Clearance of Apoptotic Cells

Tanaka

Doe

Horstmann

et al. 2014

Journal of Biological Chemistry

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Background: Serotonin (5-HT) contributes to the pathogenesis of chronic inflammatory diseases known to have defects in apoptotic cell removal (i.e. efferocytosis). Results: 5-HT impairs macrophage efferocytosis via 5-HT transporter-dependent activation of the RhoA/Rho kinase pathway. Conclusion: Results show a novel mechanism by which 5-HT might disrupt resolution of inflammation. Significance: Targeting the 5-HT transporter may have a therapeutic role in chronic inflammatory disorders.

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Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice

Cited by 67 publications

References 45 publications

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension

Neuroendocrine Signaling Via the Serotonin Transporter Regulates Clearance of Apoptotic Cells

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