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Noninvasive
System for Evaluating the Allergen-Specific Airway Response in a Murine
Model of Asthma |
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Makoto Dohi,
Shun-ichi Tsukamoto, Toshifumi Nagahori, Kazuhiko Shinagawa, Kazuko Saitoh,
Yasuko Tanaka, Shyo-ko Kobayashi, Ryoichi Tanaka, Yasuo To, and Kazuhiko
Yamamoto |
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Department
of Allergy and Rheumatology, Graduate School of Medicine, University of
Tokyo, Tokyo, Japan |
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SUMMARY: In the present
report, we show that the enhanced pause (Penh), a novel indicator of airway
responsiveness to bronchoconstrictors, can also be a good marker of airway
response to an allergen challenge in a murine model of asthma. Male BALB/c
mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal
injection and aerosol inhalation. After this immunization, the OVA-specific
IgE titer in serum increased to a significantly higher level than in a saline/PBS-treated
control group. After the final OVA aerosol challenge, Penh was repeatedly
measured in conscious, unrestrained mice, according to the time schedule.
Penh increased gradually after the challenge and reached a maximal value
at 24 hours that was significantly higher than the control value (p
< 0.01). Histologic examination of the lung revealed airway inflammation
with an invasion by eosinophils and lymphocytes from vessels into the peribronchial
interstitium and the mucosal and submucosal areas of the bronchus. There
was a strong correlation between the Penh value and eosinophil number in
bronchoalveolar lavage fluid (r = 0.699, p < 0.0001). Moreover,
Penh also correlated strongly with the intensity score of histologic findings.
These results suggest that the bronchial response to a specific allergen
could be followed in a particular individual through the noninvasive Penh
method, and that Penh accurately reflects the intensity of eosinophilic
bronchial inflammation. This system would be applicable to a noninvasive,
chronological evaluation of various experimental interventions in a murine
model of asthma. |
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