title: Toll-like receptor 4 ligand can differentially modulate the release of cytokines by human platelets.
abstract: Blood platelets link the processes of haemostasis and inflammation. This study examined the immunomodulatory factors released by platelets after Toll-Like Receptor 4 (TLR4) engagement on their surfaces. Monoclonal anti-human FcgammaRII Ab (IV.3)-treated human platelets were cultured with TLR4 ligands in the presence or absence of blocking monoclonal antibody to human TLR4. The release of sCD62p, epidermal growth factor (EGF), transforming growth factor beta (TGFbeta), interleukin (IL)-8, platelet activating factor 4 (PAF4), platelet-derived growth factor, alpha, beta polypeptide (PDGF-AB), Angiogenin, RANTES (regulated upon activation, normal T-cell expressed, and presumably secreted) and sCD40L were measured by specific enzyme-linked immunosorbent assay. TLR4 ligand [Escherichia coli lipopolysaccharide (LPS)] bound platelet TLR4, which differentially modulates the release of cytokines by platelets. It was noted that (i) sCD62p, IL-8, EGF and TGFbeta release were each independent of platelet activation after TLR4 engagement; (ii) RANTES, Angiogenin and PDGF-AB concentration were weaker in platelet supernatant after TLR4 engagement; (iii) sCD40L and PAF4 are present in large concentration in the releaseate of platelets stimulated by TLR4 ligand. The effects of LPS from E. coli on the modulation of secretory factors were attenuated by preincubation of platelets with an anti-TLR4 monoclonal antibody, consistent with the immunomodulation being specifically mediated by the TLR4 receptor. We propose that platelets adapt the subsequent responses, with polarized cytokine secretion, after TLR4 involvement.
authors.affiliation: EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cognasse
authors.forename: Hind
authors.initials: H
authors.lastname: Hamzeh-Cognasse
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lafarge
authors.forename: Olivier
authors.initials: O
authors.lastname: Delezay
authors.forename: Bruno
authors.initials: B
authors.lastname: Pozzetto
authors.forename: Archie
authors.initials: A
authors.lastname: McNicol
authors.forename: Olivier
authors.initials: O
authors.lastname: Garraud
mesh_terms: D015703:Antigens, CD / Q000097:blood; D001792:Blood Platelets / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D015539:Platelet Activation / Q000276:immunology; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; C495345:TLR4 protein, human; D060149:Tetraspanin 30; D051197:Toll-Like Receptor 4