Ovalbumin-induced airway inflammation and fibrosis in mice also exposed to ozone
Ovalbumin-induced airway inflammation and fibrosis in mice also exposed to ozone
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DOI：
10.1080/08958370490258237
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发表时间：
2004-01-01
影响因子：
2.1
通讯作者：
Kenyon, NJ
中科院分区：
文献类型：
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作者：
Last, JA;Ward, R;Kenyon, NJ
本研究采用小鼠过敏原诱导的气道炎症模型来研究臭氧暴露对气道炎症和重塑的影响。致敏BALB/c小鼠在暴露于0.2 ppm或0.5 ppm臭氧2周之前和之后分别暴露于卵清蛋白气溶胶4周。其他组小鼠暴露于卵清蛋白气溶胶6周，在第1-6周期间连续同时暴露于臭氧，或间歇同时暴露于臭氧。通过肺灌洗细胞的定量鉴别评价和染色肺切片的组织学评价来检测肺部炎症。通过显微解剖气道的定量生化分析来评估肺结构的改变（气道纤维化）。在单独暴露于卵清蛋白4周或暴露于卵清蛋白4周的动物的洗胃液中，在暴露于0.2或0.5 ppm臭氧2周之前或之后立即暴露于卵清蛋白4周，观察到细胞总数相同。小鼠暴露于卵白蛋白6周，同时在第3-6周暴露于0.2 ppm或0.5 ppm的臭氧中，通过灌洗恢复的细胞总数显著减少。在第3-6周暴露于卵清蛋白加0.2 ppm臭氧的小鼠中，观察到仅暴露于卵清蛋白气溶胶的小鼠的细胞数量低至7%。单独暴露于卵清蛋白的小鼠的洗洗液中的细胞差异计数与在所有研究方案下暴露于卵清蛋白和臭氧的小鼠的值相比有显著差异。在卵清蛋白暴露前给予臭氧2周（实验1），肺灌洗液中巨噬细胞百分比高，淋巴细胞和嗜酸性粒细胞百分比低。卵清蛋白暴露后给予臭氧2周（实验2），肺灌洗液中巨噬细胞百分比中等，嗜酸性粒细胞百分比较低，淋巴细胞百分比较高。当臭氧和卵清蛋白同时给予时（实验3和4），在0.2 ppm臭氧的灌洗液中巨噬细胞百分比高，嗜酸性粒细胞百分比高。臭氧似乎可以对抗卵清蛋白暴露的特定炎症效应，特别是在暴露于卵清蛋白之前或期间给予。采用两种不同的定量方法检测气道重塑。同时暴露于卵清蛋白和臭氧的组与单独暴露于卵清蛋白的匹配组相比，气道胶原蛋白含量没有显著增加。研究结果与同时暴露于卵清蛋白和臭氧的小鼠的加性反应一致。单独暴露于臭氧6周不会影响气道中杯状细胞的数量，而单独暴露于卵清蛋白气溶胶6周的小鼠在其传导气道中约有25%的杯状细胞。同时暴露于卵清蛋白和0.2 ppm臭氧中会导致暴露小鼠导气管中杯状细胞显著增加（占细胞总数的43%）。我们的结论是，当卵清蛋白诱导的过敏原诱导的气道炎症小鼠也暴露于臭氧时，肺部炎症反应可能会改变，但这种改变的反应取决于暴露的顺序和暴露的臭氧浓度。在测试臭氧浓度时，我们没有看到气道纤维化的变化。然而，同时暴露于卵清蛋白和0.2 ppm臭氧的小鼠中，杯状细胞增生似乎增加了。
A murine model of allergen-induced airway inflammation was used to examine the effects of exposure to ozone on airway inflammation and remodeling. Sensitized BALB/c mice were exposed to ovalbumin aerosol for 4 wk before and after 2 wk of exposure to either 0.2 ppm or 0.5 ppm ozone. Other groups of mice were exposed to ovalbumin aerosol for 6 wk with continuous concurrent exposure to ozone during wk 1-6, or during intermittent concurrent exposure to ozone. Lung inflammation was measured by quantitative differential evaluation of lung lavage cells and by histological evaluation of stained lung sections. Alterations in lung structure (airway fibrosis) were evaluated by quantitative biochemical analysis of microdissected airways. The same total number of cells was observed in lavage fluid from animals exposed for 4 wk to ovalbumin alone or to ovalbumin for 4 wk immediately before or after exposure to 2 wk of 0.2 or 0.5 ppm ozone. Mice exposed to ovalbumin for 6 wk with concurrent exposure to either 0.2 ppm or 0.5 ppm ozone during wk 3-6 had a significant decrease in the total number of cells recovered by lavage. Values as low as 7% of the cell number found in mice exposed to ovalbumin aerosol alone were observed in the mice exposed to ovalbumin plus 0.2 ppm ozone during wk 3-6. There were significant differences in the cell differential counts in the lavage fluid from mice exposed to ovalbumin alone as compared with values from mice exposed to ovalbumin and ozone under all of the protocols studied. When ozone was given for 2 wk prior to ovalbumin exposure (Experiment 1), there were a high percentage of macrophages and low percentages of lymphocytes and eosinophils in the lung lavage. When ozone was given for 2 wk after ovalbumin exposure (Experiment 2), there were a moderate percentage of macrophages, a low percentage of eosinophils, and a high percentage of lymphocytes in the lung lavage. When ozone and ovalbumin were given simultaneously (Experiments 3 and 4), there were a high percentage of macrophages in the lavage with 0.2 ppm ozone and a high percentage of eosinophils. Ozone appears to antagonize the specific inflammatory effects of ovalbumin exposure, especially when given before or during exposure to ovalbumin. Airway remodeling was examined by two different quantitative methods. None of the groups exposed concurrently to ovalbumin and ozone had a significant increase in airway collagen content as compared to the matched groups of mice exposed to ovalbumin alone. The findings were consistent with an additive response of mice to simultaneous exposure to ovalbumin and ozone. Ozone exposure alone for 6 wk did not affect the number of goblet cells in the airways, while mice exposed to ovalbumin aerosol alone for 6 wk had about 25 % goblet cells in their conducting airways. Concurrent exposure to ovalbumin and 0.2 ppm ozone caused significant increases in goblet cells (to 43% of total cells) in the conducting airways of the exposed mice. We conclude that when mice with allergen-induced airway inflammation induced by ovalbumin are also exposed to ozone, the lung inflammatory response may be modified, but that this altered response is dependent on the sequence of exposure and the concentration of ozone to which they are exposed. At the concentrations of ozone tested, we did not see changes in airway fibrosis. However, goblet-cell hyperplasia appeared to be increased in mice exposed concurrently to ovalbumin and 0.2 ppm ozone.