Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation

G. R. Zosky, A. N. Larcombe, O. J. White, J. T. Burchell, T. Z. Janosi, Z. Hantos, P. G. Holt, P. D. Sly, D. J. Turner

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Background: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. Objective: To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. Methods: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. Results: An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. Conclusions: The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalClinical and Experimental Allergy
Volume38
Issue number5
DOIs
Publication statusPublished - May 2008

Fingerprint

Ovalbumin
Allergens
Inhalation
Aerosols
Asthma
Lung
Bronchoalveolar Lavage
Mechanics
Methacholine Chloride
Immunoglobulin E
Chronic Disease
Enzyme-Linked Immunosorbent Assay
Cytokines
Serum

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • Early-phase response
  • Late-phase response
  • Mouse model

ASJC Scopus subject areas

  • Immunology

Cite this

Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation. / Zosky, G. R.; Larcombe, A. N.; White, O. J.; Burchell, J. T.; Janosi, T. Z.; Hantos, Z.; Holt, P. G.; Sly, P. D.; Turner, D. J.

In: Clinical and Experimental Allergy, Vol. 38, No. 5, 05.2008, p. 829-838.

Research output: Contribution to journalArticle

Zosky, G. R. ; Larcombe, A. N. ; White, O. J. ; Burchell, J. T. ; Janosi, T. Z. ; Hantos, Z. ; Holt, P. G. ; Sly, P. D. ; Turner, D. J. / Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation. In: Clinical and Experimental Allergy. 2008 ; Vol. 38, No. 5. pp. 829-838.
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T1 - Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation

AU - Zosky, G. R.

AU - Larcombe, A. N.

AU - White, O. J.

AU - Burchell, J. T.

AU - Janosi, T. Z.

AU - Hantos, Z.

AU - Holt, P. G.

AU - Sly, P. D.

AU - Turner, D. J.

PY - 2008/5

Y1 - 2008/5

N2 - Background: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. Objective: To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. Methods: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. Results: An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. Conclusions: The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.

AB - Background: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. Objective: To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. Methods: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. Results: An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. Conclusions: The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.

KW - Airway hyperresponsiveness

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KW - Late-phase response

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