title: Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice.
abstract: BACKGROUND
  Mast cells, IgE, and TNF, which have been implicated in human atopic asthma, contribute significantly to the allergic airway inflammation induced by ovalbumin (OVA) challenge in mice sensitized with OVA without alum. However, it is not clear to what extent mast cells represent a significant source of TNF in this mouse model.
  
  
  OBJECTIVE
  We investigated the importance of mast cell-derived TNF in a mast cell-dependent model of OVA-induced airway hyperreactivity (AHR) and allergic airway inflammation.
  
  
  METHODS
  Features of this model of airway inflammation were analyzed in C57BL/6J-wild-type mice, mast cell-deficient C57BL/6J-Kit(W-sh)(/W-sh) mice, and C57BL/6J Kit(W-sh/W-sh) mice that had been systemically engrafted with bone marrow-derived cultured mast cells from C57BL/6J-wild-type or C57BL/6J-TNF(-/-) mice.
  
  
  RESULTS
  Ovalbumin-induced AHR and airway inflammation were significantly reduced in mast cell-deficient Kit(W-sh/W-sh) mice versus wild-type mice. By contrast, Kit(W-sh/W-sh) mice that had been engrafted with wild-type but not with TNF(-/-) bone marrow-derived cultured mast cells exhibited responses very similar to those observed in wild-type mice. Mast cells and mast cell-derived TNF were not required for induction of OVA-specific memory T cells in the sensitization phase, but significantly enhanced lymphocyte recruitment and T(H)2 cytokine production in the challenge phase.
  
  
  CONCLUSIONS
  Mast cell-derived TNF contributes significantly to the pathogenesis of mast cell-dependent and IgE-dependent, OVA-induced allergic inflammation and AHR in mice, perhaps in part by enhancing lymphocyte recruitment and T(H)2 cytokine production.
  
  
  CONCLUSIONS
  Our findings in mice support the hypothesis that mast cell-derived TNF can promote allergic inflammation and AHR in asthma.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Lien H
authors.initials: LH
authors.lastname: Ho
authors.forename: Mang
authors.initials: M
authors.lastname: Yu
authors.forename: Rossella
authors.initials: R
authors.lastname: Monteforte
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D009195:Peroxidase