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

Item Type:Article
Title:Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice
Creators Name:Duerschmied, D. and Suidan, G.L. and Demers, M. and Herr, N. and Carbo, C. and Brill, A. and Cifuni, S.M. and Mauler, M. and Cicko, S. and Bader, M. and Idzko, M. and Bode, C. and Wagner, D.D.
Abstract:The majority of peripheral serotonin is stored in platelets, which release it upon activation. Serotonin releases Weibel-Palade bodies (WPB) 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 as compared to 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 WPB, 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, while 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.
Keywords:Serotonin, Neutrophils, Inflammation, Platelets, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:121
Number:6
Page Range:1008-1015
Date:7 February 2013
Official Publication:https://doi.org/10.1182/blood-2012-06-437392
PubMed:View item in PubMed

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