title: Activated protein C modulates the proinflammatory activity of dendritic cells.
abstract: BACKGROUND
  Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells.
  
  
  METHODS
  Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells.
  
  
  RESULTS
  Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice.
  
  
  CONCLUSIONS
  These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation.
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; BONAC Corporation, BIO Factory 4F, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushima
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Ziaurahman
authors.initials: Z
authors.lastname: Roeen
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Corina N
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Josephine A
authors.initials: JA
authors.lastname: Hinneh
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; Iwade Research Institute of Mycology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Harada
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yasuma
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan ; Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Urawa
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan.
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
keywords: allergy; coagulation; dendritic cells; protein C pathway