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

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Item Type:	Article
Title:	Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice
Creators Name:	Duerschmied, D., Suidan, G.L., Demers, M., Herr, N., Carbo, C., Brill, A., Cifuni, S.M., Mauler, M., Cicko, S., Bader, M., Idzko, M., 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
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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