title: Mast Cell Deficiency Limits the Development of Chronic Rhinosinusitis in Mice.
abstract: BACKGROUND
  Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in adults in both developing and developed countries. The etiology and pathogenesis of CRS remain poorly understood, and the disease is refractory to therapy in many patients. Mast cell activation has been demonstrated in the sinonasal mucosa of patients with CRS; however, the specific contribution of mast cells to the development and pathogenesis of this disease has not been established.
  
  
  OBJECTIVE
  The objective of this study was to investigate the role of mast cells in the development of CRS.
  
  
  METHODS
  C57BL/6 wild-type and C57BL/6-Kit(W-sh/W-sh) mast cell-deficient mice were immunized by intraperitoneal allergen injection and subsequent chronic low dose intranasal allergen challenges. The sinonasal phenotypes of these groups were then evaluated and compared to saline-treated controls using radiologic, histologic, and immunologic methods.
  
  
  RESULTS
  Wild-type mice exposed to chronic intranasal allergen developed many features seen in human CRS, including mucosal thickening, cystic changes, polyp development, eosinophilia, goblet cell hyperplasia, and mast cell activation. In contrast, sinonasal pathology was significantly attenuated in mast cell-deficient mice subjected to the same chronic allergen protocol. Specifically, tissue eosinophilia and goblet cell hyperplasia were reduced by approximately 50% compared to wild-type levels. Surprisingly, none of the mast cell-deficient mice subjected to chronic allergen challenge developed cystic changes or polypoid changes in the nose or sinuses.
  
  
  CONCLUSIONS
  These data identify a critical role for mast cells in the development of many features of a mouse model of eosinophilic CRS, suggesting that therapeutic strategies targeting mast cells be examined in humans afflicted with this disease.
authors.affiliation: Department Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Naselsky
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Corey M
authors.initials: CM
authors.lastname: Jania
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Chason
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Julianne J
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Doerschuk
authors.affiliation: Department Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Graham
authors.affiliation: Department of Otolaryngology Head Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Senior
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA stephen_tilley@med.unc.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
mesh_terms: D000485:Allergens / Q000633:toxicity; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced / Q000276:immunology; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia; D008407:Mast Cells / Q000276:immunology*; D008443:Maxillary Sinus / Q000000981:diagnostic imaging / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009298:Nasal Polyps / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000633:toxicity; D010256:Paranasal Sinuses / Q000000981:diagnostic imaging / Q000473:pathology; D012220:Rhinitis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D012852:Sinusitis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D000485:Allergens; D010047:Ovalbumin
keywords: mast cell; mouse model; nasal polys; pathogenesis; rhinosinusitis