title: Serotonin is a key factor for mouse red blood cell survival.
abstract: Serotonin (5-HT) is a monoamine originally purified from blood as a vasoactive agent. In nonneuronal tissues, its presence is linked with the expression of tryptophan hydroxylase 1 (TPH1) that catalyzes the rate-limiting step of its synthesis. Targeted disruption in mice of the TPH1 gene results in very low levels of circulating 5-HT. Previous analysis of the TPH1 knockout (TPH1(-/-)) mouse revealed that they develop a phenotype of macrocytic anemia with a reduced half-life of their circulating red blood cells (RBC). In this study, to establish whether the observed reduced half-life of TPH1(-/-) RBC is an intrinsic or an extrinsic characteristic, we compared their survival to RBC isolated from wild-type mice. Both in vivo and in vitro data converge to demonstrate an extrinsic protective effect of 5-HT since presence of 5-HT in the RBC environment protects RBC from senescence. The protective effect played by 5-HT is not mediated through activation of a classical pharmacological pathway as no 5-HT receptors were detected on isolated RBC. Rather, 5-HT acts as an effective antioxidant since reduction of 5-HT circulating levels are associated with a decrease in the plasma antioxidant capacity. We further demonstrate a link between oxidation and the removal of damaged RBC following transfusion, as supplementation with 5-HT improves RBC post-transfusion survival in a mouse model of blood banking.
authors.affiliation: Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, CNRS UMR 8147, Hôpital Universitaire Necker Enfants Malades, Paris, France ; Laboratoire d'excellence GR-Ex, Paris, France ; Inserm UMR_S665, Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Amireault
authors.affiliation: Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, CNRS UMR 8147, Hôpital Universitaire Necker Enfants Malades, Paris, France ; Laboratoire d'excellence GR-Ex, Paris, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bayard
authors.affiliation: Service de Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.affiliation: Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, CNRS UMR 8147, Hôpital Universitaire Necker Enfants Malades, Paris, France ; Laboratoire d'excellence GR-Ex, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Sibon
authors.affiliation: Laboratoire d'excellence GR-Ex, Paris, France ; Inserm UMR_S665, Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
authors.affiliation: Laboratoire d'excellence GR-Ex, Paris, France ; Inserm UMR_S665, Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin
authors.affiliation: Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, CNRS UMR 8147, Hôpital Universitaire Necker Enfants Malades, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.affiliation: Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, CNRS UMR 8147, Hôpital Universitaire Necker Enfants Malades, Paris, France ; Laboratoire d'excellence GR-Ex, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, CNRS UMR 8147, Hôpital Universitaire Necker Enfants Malades, Paris, France ; Laboratoire d'excellence GR-Ex, Paris, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Côté
mesh_terms: D000748:Anemia, Macrocytic / Q000235:genetics / Q000473:pathology; D000818:Animals; D001793:Blood Preservation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D006085:Graft Survival / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012701:Serotonin / Q000494:pharmacology*; D013696:Temperature; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase