title: Cutting edge: T cells trigger CD40-dependent platelet activation and granular RANTES release: a novel pathway for immune response amplification.
abstract: Platelets, in addition to exerting hemostatic activity, contribute to immunity and inflammation. The recent report that platelets express CD40 led us to hypothesize that CD40 ligand (CD40L)-positive T cells could bind to platelets, cause their activation, and trigger granular RANTES release, creating a T cell recruitment feedback loop. Platelets were cocultured with resting or activated autologous T cells and their activation was assessed by P-selectin expression. RANTES binding to endothelial cells was assessed by confocal microscopy, and its biological activity was demonstrated by a T cell adhesion assay. CD40L-positive T cells induced platelet activation through a contact-mediated, CD40-dependent pathway resulting in RANTES release, which bound to endothelial cells and mediated T cell recruitment. Soluble CD40L induced the same events via p38, but not extracellular signal-regulated kinase, phosphorylation. These results show the existence of a novel platelet-dependent pathway of immune response amplification which brings these nonimmune cells close to the level of pathogenic relevance traditionally attributed to classical immune cells.
authors.affiliation: Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.forename: Carol
authors.initials: C
authors.lastname: de la Motte
authors.forename: Brenda M Rivera
authors.initials: BM
authors.lastname: Reyes
authors.forename: Miquel
authors.initials: M
authors.lastname: Sans
authors.forename: Alan D
authors.initials: AD
authors.lastname: Levine
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiocchi
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D001792:Blood Platelets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000502:physiology*; D023201:CD40 Ligand / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism* / Q000502:physiology; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000276:immunology* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D015539:Platelet Activation / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D018946:Chemokine CCL5; D023201:CD40 Ligand; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases