Fig. 3. HDM-treated Adam8^−/− mice have greater AAI and higher AHR than HDM-treated WT mice.

BALB/c WT and BALB/c Adam8^−/− mice were sensitized and challenged via the intranasal route with HDM protein extract or sham-treated with PBS as a control. In A, leukocytes were counted in BAL samples 72 h after the last HDM challenge. Data are mean ± SEM; n= 5 PBS-treated mice and n = 10–12 HDM-treated mice. Asterisk indicates p ≤ 0.007 versus PBS-treated mice belonging to the same genotype as the OVA-treated mice, and ** indicates p = 0.017. B shows sections of lungs fixed and inflated in formalin and stained with hematoxylin and eosin. Upper panels in B show greater peribronchial inflammation (arrows) in HDM-treated Adam8^−/− mice compared with HDM-treated WT mice. Lower panels in B show that there is predominantly eosinophilic peribronchial inflammation in both genotypes (arrowheads). In C, HMD- or PBS-treated BALB/c WT and BALB/c Adam8^−/− mice were exposed to varying concentrations of aerosolized methacholine (or aerosolized PBS) and Rn was measured 72 h after the last HDM challenge. Data are mean ± SEM; n = 5–6 mice/group for PBS-treated mice and n = 7–8 mice per group for HDM-treated mice. Asterisk indicates p < 0.001 when compared with HDM-treated WT mice; and ** indicates p ≤ 0.036 when compared with PBS-treated mice belonging to the same genotype as the OVA-treated mice. Responses for HDM-treated WT mice ranged from 0.17–0.43 cm H₂O/s/ml for 1 mg/ml of methacholine; 0.27–0.50 cm H₂O/s/ml for 3 mg/ml of methacholine; and 0.40–1.06 cm H₂O/s/ml for 10 mg/ml of methacholine; 0.64–1.44 cm H₂O/s/ml for 30 mg/ml of methacholine; and 0.66–1.34 cm H₂O/s/ml for 45 mg/ml methacholine. Responses for HDM treated Adam8^−/− mice ranged from 0.26–0.71 cm H₂O/s/ml for 1 mg/ml of methacholine; 0.26–1.64 cm H₂O/s/ml for 3 mg/ml of methacholine; 0.48–1.71 cm H₂O/s/ml for 10 mg/ml methacholine; 0.86–2.11 cm H₂O/s/ml for 30 mg/ml methacholine; and 1.37–1.93 cm H₂O/s/ml for 45 mg/ml methacholine.