title: Mast cells contribute to double-stranded RNA-induced augmentation of airway eosinophilia in a murine model of asthma.
abstract: BACKGROUND
  Clinical studies showed the contribution of viral infection to the development of asthma. Although mast cells have multiple roles in the pathogenesis of allergic asthma, their role of in the virus-associated pathogenesis of asthma remains unknown. Most respiratory viruses generate double-stranded (ds) RNA during their replication. dsRNA provokes innate immune responses. We recently showed that an administration of polyinocinic polycytidilic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13.
  
  
  METHODS
  The effect of poly IC on allergen-induced airway eosinophilia was investigated for mast cell-conserved Kit+/+ mice and -deficient KitW/KitW-v mice. The outcome of mast cell reconstitution was further investigated.
  
  
  RESULTS
  Airway eosinophilia and IL-13 production were augmented by poly IC in Kit+/+ mice but not in KitW/KitW-v mice. When KitW/KitW-v mice were reconstituted with bone marrow-derived mast cells (BMMCs), the augmentation was restored. The augmentation was not induced in the mice systemically deficient for TIR domain-containing adaptor-inducing IFN-β (TRIF) or interferon regulatory factor (IRF)-3, both mediate dsRNA-triggered innate immune responses. The augmentation was, however, restored in KitW/KitW-v mice reconstituted with TRIF-deficient or IRF-3-deficient BMMCs. Although leukotriene B4 and prostaglandin D2 are major lipid mediators released from activated mast cells, no their contribution was shown to the dsRNA-induced augmentation of airway eosinophilia.
  
  
  CONCLUSIONS
  We conclude that mast cells contribute to dsRNA-induced augmentation of allergic airway inflammation without requiring direct activation of mast cells with dsRNA or involvement of leukotriene B4 or prostaglandin D2.
authors: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Keiko
authors: K
authors: Kan-o
authors: Yuko
authors: Y
authors: Matsunaga
authors: Satoru
authors: S
authors: Fukuyama
authors: Atsushi
authors: A
authors: Moriwaki
authors: Hiroko
authors: H
authors: Hirai-Kitajima
authors: Takehiko
authors: T
authors: Yokomizo
authors: Kosuke
authors: K
authors: Aritake
authors: Yoshihiro
authors: Y
authors: Urade
authors: Yoichi
authors: Y
authors: Nakanishi
authors: Hiromasa
authors: H
authors: Inoue
authors: Koichiro
authors: K
authors: Matsumoto
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008407:Mast Cells / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011070:Poly I-C / Q000633:toxicity; D012330:RNA, Double-Stranded / Q000235:genetics*
chemical_list: D012330:RNA, Double-Stranded; D011070:Poly I-C