title: The pattern of methacholine responsiveness in mice is dependent on antigen challenge dose.
abstract: BACKGROUND
  Considerable variation exists in the protocols used to induce hyperresponsiveness in murine models of allergic sensitisation. We examined the effect of varying the number of antigen exposures at challenge on the development of methacholine responsiveness in systemically sensitised mice.
  
  
  METHODS
  BALB/c mice were sensitised with ovalbumin (OVA), challenged with 1, 3 or 6 OVA aerosols. Lung function was measured using low frequency forced oscillations and partitioned into components representing the airways (Raw) and lung parenchyma (tissue damping (G) and tissue elastance (H)). Responsiveness to inhaled methacholine (MCh), inflammatory cell profile and circulating IgE were assessed 24 and 48 hours after challenge. The threshold dose of MCh required to elicit a detectable response (sensitivity) and response to 30 mg x mL(-1) (maximal response) were determined for each compartment.
  
  
  RESULTS
  Sensitivity; All three OVA protocols resulted in an increased sensitivity to MCh in Raw but not in G or H. These responses where present at 24 and 48 hrs, except 1 OVA aerosol in which changes had resolved by 48 hrs. Maximal response; 1 OVA aerosol increased maximal responses in Raw, G and H at 24 hrs, which was gone by 48 hrs. Three OVA aerosols increased responses in H at 48 hrs only. Six OVA challenges caused increases in Raw, G and H at both 24 and 48 hrs. Eosinophils increased with increasing antigen challenges. IgE was elevated by OVA sensitisation but not boosted by OVA aerosol challenge.
  
  
  CONCLUSIONS
  The pattern of eosinophilia, IgE and MCh responsiveness in mice was determined by antigen dose at challenge. In this study, increased sensitivity to MCh was confined to the airways whereas increases in maximal responses occurred in both the airway and parenchymal compartments. The presence of eosinophilia and IgE did not always coincide with increased responsiveness to inhaled MCh. These findings require further systematic study to determine whether different mechanisms underlie airway and parenchymal hyperresponsiveness post antigen challenge.
authors.affiliation: Telethon Institute for Child Health Research, West Perth, 6872, Australia. graemez@ichr.uwa.edu.au
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Turner
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000941:Antigens; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010047:Ovalbumin