title: Platelets, after exposure to a high shear stress, induce IL-10-producing, mature dendritic cells in vitro.
abstract: There is evidence for immune system involvement in atherogenesis. In the present study the effect of platelets on dendritic cells (DC), an important immunologic regulator, was examined in vitro. Platelet-rich plasma, after exposure to shear stress, was added to human monocyte-derived immature DC, which were then examined for surface Ag expression, allogeneic T lymphocyte stimulatory activity, and cytokine production. After exposure, the number of anti-CD40 ligand (anti-CD40L) and anti-P-selectin IgG molecules bound per platelet was increased. These activated platelets induced DC maturation, as revealed by significant up-regulation of CD83, CD80, and CD86 Ags. The addition of platelets in the presence of IFN-gamma plus LPS significantly enhanced IL-10 production from immature DC. After platelet addition, mature DC provoked a significant proliferation of allogeneic naive T lymphocytes. These activated T cells showed lower IFN-gamma production than those stimulated by LPS- and IFN-gamma-treated DC. CD40L on the platelet surface was not involved in maturation of DC, as mAb to CD40L failed to block maturation. The effect of platelets was observed even if platelets and DC were separated using large pore-sized membranes or when platelets were depleted from plasma by centrifugation. Furthermore, it was abrogated after the depletion of protein fraction. Thus, soluble protein factors excreted from activated platelets contribute to IL-10-producing DC maturation.
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan. masaoha@is.ic.u-tokai.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Hagihara
authors.forename: Ayako
authors.initials: A
authors.lastname: Higuchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Tamura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ueda
authors.forename: Kaori
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
authors.forename: Shunnosuke
authors.initials: S
authors.lastname: Handa
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis; D019007:P-Selectin / Q000096:biosynthesis; D015539:Platelet Activation / Q000276:immunology; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014783:Viscosity
chemical_list: D015848:Interleukin-5; D007519:Isoantigens; D008565:Membrane Proteins; D019007:P-Selectin; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma