Serotonin is a key factor for mouse red blood cell survival

PLoS One. 2013 Dec 17;8(12):e83010. doi: 10.1371/journal.pone.0083010. eCollection 2013.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Macrocytic / genetics
  • Anemia, Macrocytic / pathology
  • Animals
  • Blood Preservation / methods
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Dose-Response Relationship, Drug
  • Erythrocyte Transfusion
  • Erythrocytes / drug effects*
  • Erythrocytes / physiology
  • Graft Survival / drug effects
  • Hemolysis / drug effects
  • Hemolysis / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Serotonin / pharmacology*
  • Temperature
  • Tryptophan Hydroxylase / genetics

Substances

  • Serotonin
  • Tph1 protein, mouse
  • Tryptophan Hydroxylase

Grants and funding

PA was supported by the Institut Arnault Tzanck and the Fédération Française du Don de Sang Bénévole. This work was supported by grants from la Ligue contre le Cancer (to OH and FC) and l’Association Recherche Transfusion (to PA). This study was supported by grants from Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051. The labex GR-Ex is funded by the program “Investissements d’avenir” of the French National Research Agency, reference ANR-11-IDEX-0005-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.