[Effects of ozone oxidative stress on the airway hyperresponsiveness and mucus production in mice with acute allergic airway inflammation].
OBJECTIVE
To explore the impact of ozone on the airway hyperresponsinveness (AHR), airway inflammation and mucus production in an allergic asthma mouse model.


METHODS
Twenty-eight female BALB/c mice were randomly divided into 4 equal groups: healthy control, ozone control, asthma model, and ozone intervention. For asthma model establishing, the mice were sensitized and challenged with ovalbumin, while the controls received saline. For ozone exposure, the mice were exposed to 2.0 ppm ozone for 3 hrs, while the control treatment group exposed to filtered air for 3 hrs. Some measurements were performed 24 hrs after the exposure, including AHR, pulmonary inflammation, mucus secretion, epithelial barrier function, and the level of oxidant stress.


RESULTS
Compared with the asthma model group, mice in the ozone intervention group exhibited lower LogPC100Penh (0.22 ± 0.09 vs 0.50 ± 0.19, t = 3.06, P = 0.006), higher bronchoalveolar lavage (BAL) neutrophil numbers [(0.80 ± 0.21) x 10(3)/L vs (0.15 ± 0.06) x 10(3)/L, t = 3.63, P = 0.019] and BAL concentration of lower molecular weight hyaluronan (LMW-HA) [(111 ± 17) µg/L vs (35 ± 18) µg/L, t = 5.12 P = 0.000], TNF-α[(155 ± 30) µg/L vs (86 ±19) µg/L, t = 2.15, P = 0.044] and IL-13 [(65 ± 11) µg/L vs (33 ± 20) µg/L, t = 2.95, P = 0.008]. Mice in the ozone intervention group showed higher lung pathological inflammation score (2. 80 0.10 vs 1.92 ± 0.23, t =3.91, P = 0.000) and upregulated expressions of TNF-α mRNA (7.0 ± 1.5 vs 3.57 ± 1.20, t = 2.65, P = 0.014), CXCL-1 mRNA (7.0 ± 1.1 vs 2.5 ± 1.0, t = 4.12, P = 0.000) and IL-17 mRNA (28.8 ± 5.2 vs 16.4 ± 4.4, t = 6.33, P = 0.000). Ozone exposure on the asthmatic mice also caused higher percentage of PAS positive-staining epithelial cells [(76.2 ± 8.7) % vs (55.8 ± 14.4) %, t = 8.14, P = 0.000] and higher epithelial surface mucus volume [(721 ± 584) nl/mm2 vs (272 ± 185) nl/mm2, t = 5.78, P = 0.000] as well as the MUC5ac mRNA expression (15.4 ± 4.6 vs 7.0 ± 1.9, t = 4.37, P = 0.000). Besides, ozone exposure in the asthma model decreased epithelial cell density (82 ± 22 vs 116 ± 15, t = -10.1, P = 0.000), while increased the BAL concentration of albumin [(45 ± 6) g/L vs (33 ± 4) g/L, t = 3.89, P = 0.001] .


CONCLUSIONS
Ozone exaggerates AHR and pulmonary inflammation, and causes damages in epithelial cells and promotes the production of epithelial mucus.
Bao
B
Aihua
Chen
C
Yuqing
Min
M
Zhang
Li
L
Feng
Zhou
Z
Xin
D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism*; D010047:Ovalbumin; D018384:Oxidative Stress; D010126:Ozone / Q000009:adverse effects*; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012137:Respiratory System / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018793:Interleukin-13; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone; D010047:Ovalbumin