%0 Journal Article %T Serotonin Is a Key Factor for Mouse Red Blood Cell Survival %A Pascal Amireault %A Elisa Bayard %A Jean-Marie Launay %A David Sibon %A Caroline Le Van Kim %A Yves Colin %A Michel Dy %A Olivier Hermine %A Francine C£¿t¨¦ %J PLOS ONE %D 2013 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0083010 %X 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0083010