title: Induction, distribution and modulation of upper airway allergic inflammation in mice.
abstract: BACKGROUND
  To further elucidate mechanisms of human allergic rhinosinusitis, we studied the induction, distribution and modulation of allergen-induced upper airway inflammation in a BALB/c mouse model.
  
  
  METHODS
  Allergic inflammation induced with ovalbumin (OVA) by intraperitoneal (IP) injection in alum was compared to repeated intranasal instillation. The type and distribution of inflammatory cells was compared in the respiratory and olfactory epithelial compartments. Eosinophil distribution was assessed using Scarlet Red stain and a polyclonal antibody recognizing eosinophil major basic protein (MBP). The role of interleukin (IL)-5 in upper airway inflammation was tested by administration of polyclonal anti-IL-5 antibody during the sensitization protocol.
  
  
  RESULTS
  Unsensitized control mice receiving saline failed to develop upper airway eosinophil infiltration. IP OVA-sensitized mice developed marked upper airway mucosal eosinophil infiltration after aerosol OVA challenge, whereas repeated intranasal instillation of OVA produced qualitatively similar, but less intense eosinophil infiltration. Using either sensitization protocol, eosinophil infiltration was seen in areas of the lower portion of the nasal septum, the floor and the lower lateral walls of the mid-caudal region of the nasal cavity. Immunofluorescence staining for MBP confirmed this distribution of eosinophils but also demonstrated some eosinophils in the maxillary sinuses and in circumscribed regions of the ethmoturbinates. All areas of eosinophil infiltration were lined by respiratory epithelium. The selective infiltration of respiratory but not olfactory epithelium by eosinophils was unassociated with a measurable induction of epithelial ICAM-1 or eotaxin expression. OVA-induced upper airway eosinophil infiltration was found to be IL-5 dependent, since administration of a polyclonal anti-IL-5 antibody (TRFK-5) during OVA sensitization resulted in a marked modulation (80% decrease) in eosinophil infiltration in response to subsequent OVA challenge.
  
  
  CONCLUSIONS
  The mouse upper airway, specifically in areas containing respiratory epithelium, is a target for OVA-induced allergic inflammation. This selective infiltration of respiratory, but not olfactory, epithelium is, in part, dependent upon IL-5. This model is useful for further dissection of the inflammatory response with genetic manipulations and targeted immunological approaches.
authors.affiliation: Division of Allergy and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
authors.forename: I
authors.initials: I
authors.lastname: Hussain
authors.forename: D
authors.initials: D
authors.lastname: Randolph
authors.forename: S L
authors.initials: SL
authors.lastname: Brody
authors.forename: S K
authors.initials: SK
authors.lastname: Song
authors.forename: A
authors.initials: A
authors.lastname: Hsu
authors.forename: A M
authors.initials: AM
authors.lastname: Kahn
authors.forename: D D
authors.initials: DD
authors.lastname: Chaplin
authors.forename: D L
authors.initials: DL
authors.lastname: Hamilos
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D001985:Bronchial Provocation Tests; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology*
chemical_list: C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin