title: LPS stimulation of purified human platelets is partly dependent on plasma soluble CD14 to secrete their main secreted product, soluble-CD40-Ligand.
abstract: BACKGROUND
  Platelets are instrumental to primary haemostasis; in addition, as they are central to endothelium vascular repair, they play a role in physiological inflammation. Platelets have also been demonstrated to be key players in innate immunity and inflammation, expressing Toll-like receptors (TLRs) to sense microbial infection and initiate inflammatory responses. They are equipped to decipher distinct signals, to use alternate pathways of signalling through a complete signalosome, despite their lack of a nucleus, and to adjust the innate immune response appropriately for pathogens exhibiting different types of 'danger' signals. Previous work has described the two main LPS isoforms-TLR4 activation pathways in purified platelets. However, the precise mechanism of TLR4 signalling in platelets is not completely unravelled, especially how this signalling may occur since platelets do not express CD14, the TLR4 pathophysiological companion for LPS sensing. Thus, we investigated from what source the CD14 molecules required for TLR4 signalling in platelets could come.
  
  
  RESULTS
  Here we show that CD14, required for optimal response to LPS stimulation, is obtained from plasma, but used with restrictive regulation. These data add to the body of evidence that platelets are closer to regulatory cells than to first line defenders. The readout of our experiments is the canonical secreted cytokine-like protein, soluble (s)CD40L, a molecule that is central in physiology and pathology and that is abundantly secreted by platelets from the alpha-granules upon stimulation.
  
  
  CONCLUSIONS
  We show that sCD14 from plasma contributes to LPS/TLR4 signalling in platelets to allow significant release of soluble CD40L, thereby elucidating the mechanism of LPS-induced platelet responses and providing new insights for reducing LPS toxicity in the circulation.
authors: Université de Lyon, GIMAP-EA3064, 15 rue Ambroise Paré, 42023, Saint-Etienne, France. pauline.damien2@yahoo.fr.
authors: Pauline
authors: P
authors: Damien
authors: Université de Lyon, GIMAP-EA3064, 15 rue Ambroise Paré, 42023, Saint-Etienne, France. fabrice.cognasse@univ-st-etienne.fr.|EFS Auvergne-Loire, Saint-Etienne, France. fabrice.cognasse@univ-st-etienne.fr.
authors: Fabrice
authors: F
authors: Cognasse
authors: EFS Auvergne-Loire, Saint-Etienne, France. marie-ange.eyraud@efs.sante.fr.
authors: Marie-Ange
authors: MA
authors: Eyraud
authors: EFS Auvergne-Loire, Saint-Etienne, France. charles-antoine.arthaud@efs.sante.fr.
authors: Charles-Antoine
authors: CA
authors: Arthaud
authors: Université de Lyon, GIMAP-EA3064, 15 rue Ambroise Paré, 42023, Saint-Etienne, France. bruno.pozzetto@univ-st-etienne.fr.
authors: Bruno
authors: B
authors: Pozzetto
authors: Université de Lyon, GIMAP-EA3064, 15 rue Ambroise Paré, 42023, Saint-Etienne, France. olivier.garraud@univ-st-etienne.fr.|Institut National de la Transfusion Sanguine, Paris, France. olivier.garraud@univ-st-etienne.fr.
authors: Olivier
authors: O
authors: Garraud
authors: Université de Lyon, GIMAP-EA3064, 15 rue Ambroise Paré, 42023, Saint-Etienne, France. hind.hamzeh@univ-st-etienne.fr.
authors: Hind
authors: H
authors: Hamzeh-Cognasse
mesh_terms: D001792:Blood Platelets / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D023201:CD40 Ligand
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