title: Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice.
abstract: The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) 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 compared with 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 WPBs, 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, whereas 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.
authors.affiliation: Immune Disease Institute, Boston, MA 02115, USA. daniel.duerschmied@uniklinik-freiburg.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Duerschmied
authors.forename: Georgette L
authors.initials: GL
authors.lastname: Suidan
authors.forename: Melanie
authors.initials: M
authors.lastname: Demers
authors.forename: Nadine
authors.initials: N
authors.lastname: Herr
authors.forename: Carla
authors.initials: C
authors.lastname: Carbo
authors.forename: Alexander
authors.initials: A
authors.lastname: Brill
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Cifuni
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mauler
authors.forename: Sanja
authors.initials: S
authors.lastname: Cicko
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
mesh_terms: D000208:Acute Disease; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005473:Fluoxetine / Q000276:immunology / Q000494:pharmacology; D006632:Histamine / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D036904:Leukocyte Rolling / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012701:Serotonin / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000276:immunology / Q000494:pharmacology; D012772:Shock, Septic / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D014365:Tryptophan Hydroxylase / Q000172:deficiency / Q000235:genetics; D020302:Weibel-Palade Bodies / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D005473:Fluoxetine; D006632:Histamine; D019041:L-Selectin; D008070:Lipopolysaccharides; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase