J Korean Med Sci.  2004 Feb;19(1):69-73. 10.3346/jkms.2004.19.1.69.

Airway Inflammation and Allergen Specific IgE Production May Persist Longer Than Airway Hyperresponsiveness in Mice

• Chang YS
• Kim YK
• Kim TB
• Kang HR
• Kim SS
• Bahn JW
• Min KU
• Kim YY
• Cho SH

• KMID: 1785696
• DOI: http://doi.org/10.3346/jkms.2004.19.1.69

Abstract

During the preclinical study of new therapeutic modality, we evaluate whether the treatment can reverse the established asthma phenotypes in animal model. However, few have reported on the long term persistence of asthma phenotypes upon re-challenge with allergen (secondary challenge) in animal model. We evaluated the persistence of asthma phenotypes by secondary challenge at different times in previously challenged murine asthma model. BALB/c mice sensitized by intraperitoneal injections of 20 microgram of ovalbumin and 1 mg of alum on days 1 and 14 were challenged initially by the inhalation of 1% ovalbumin for 30 min on days 21, 22, and 23. Each group of mice was rechallenged at 5, 7, 9, or 12 weeks after the initial challenge. Airway hyperresponsiveness, BAL fluid, airway histology and serum ovalbumin-specific IgE level were evaluated. Airway eosinophilia, airway inflammation and serum ovalbumin-specific IgE production persisted upon secondary allergen challenges at least 12 weeks after the initial challenge. However, airway hyperresponsiveness persisted only until mice were rechallenged 7 weeks after the initial challenge. Airway inflammation and allergen specific IgE production may persist longer than airway hyperresponsiveness in a mouse asthma model of secondary allergen challenge.

Keyword

Asthma; Disease Models; Animal; Mice; Allergen Challenge

MeSH Terms

Allergens
Animals
Asthma/metabolism/*pathology
Bronchial Hyperreactivity/*diagnosis
Bronchoalveolar Lavage
Bronchoalveolar Lavage Fluid
Female
Immunoglobulin E/*biosynthesis/chemistry
*Inflammation
Lung/pathology
Mice
Mice, Inbred BALB C
Ovalbumin/pharmacology
Phenotype
Respiratory Hypersensitivity/*diagnosis
Respiratory System/pathology
Support, Non-U.S. Gov't
Time Factors

Figure

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  Fig. 1 Experimental protocols for sensitization, initial challenge and secondary challenge. 7-week old female BALB/c mice were used for the experiment. Mice were sensitized by intraperitoneal injection and initial provocative challenge was done on days 21, 22, 23 (0 week). Secondary challenges were performed at 5, 7, 9, or 12 weeks after the initial challenge. PBS treated mice were used as controls. Five mice were used in each group. IP: intraperitoneal injection.

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  Fig. 2 Airway hyperresponsiveness upon a secondary OVA challenge is persistent when mice were rechallenged 5 or 7 weeks after the initial inhalation challenge. However, airway hyperresponsiveness disappeared when mice were rechallenged 9 or 12 weeks after the initial challenge. The results are presented as PC200 values, where PC200 is the concentration of methacholine required to increase the baseline Penh by 200%.

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  Fig. 3 (A) The proportion of eosinophils in bronchoalveolar lavage fluid. Eosinophils are increased even when mice were rechallenged 12 weeks after the initial challenge. (*p<0.05, compared to the PBS treated mice, BALF: bronchoalveolar lavage fluid). (B) The degrees of airway inflammation observed in the initially and rechallenged animals at 5, 7, 9, or 12 weeks after the initial challenge are similar each other and higher than that of the PBS treated mice. Total lung inflammation was defined as the average value of the peribronchial and perivascular inflammation scores. (*p<0.05, compared to initially challenged mice).

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  Fig. 4 The serum ovalbumin specific IgE level is still increased when mice were rechallenged 12 weeks after the initial challenge. The level of the specific IgE in the initially challenged or rechallenged mice are similar (p>0.05, by Kruskal-Willis test) and higher than that of PBS treated group (*p<0.05, compared to all allergen challenged groups). Sera of four to five mice were evaluated in each group. BALF: bronchoalveolar lavage fluid.

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