Resistance of very young mice to inhaled allergen sensitization is overcome by coexposure to an air-pollutant aerosol.
Resistance of very young mice to inhaled allergen sensitization is overcome by coexposure to an air-pollutant aerosol.
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通过共同暴露于空气污染物气溶胶，可以克服年幼小鼠对吸入过敏原致敏的抵抗力。
DOI：
10.1164/ajrccm.161.4.9906137
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发表时间：
2000
影响因子：
24.7
通讯作者：
Kobzik,L
中科院分区：
文献类型：
--
作者：
Hamada,K;Goldsmith,CA;Goldman,A;Kobzik,L
空气污染在引发哮喘中的作用是有争议的。 我们试图通过使用非常年幼的小鼠来模拟空气污染对发育中的肺中吸入过敏原的免疫反应的潜在影响。将新生小鼠反复暴露于雾化卵清蛋白（OVA; 3%磷酸盐缓冲盐水中，10分钟/天，从第5天至第15天）。在第6、8和10天，还将一些小鼠暴露于残余油飞灰的浸出物（ROFA-s）（环境空气颗粒的替代物）30分钟。将非常年幼的小鼠反复暴露于单独的变应原（OVA）或单独的污染物（ROFA-s）对气道高反应性（AHR，在16日龄时用无创体积描记法测量为增强的暂停（Penh））没有影响，并且不会引起炎症或OVA特异性抗体产生。成年小鼠单独暴露于OVA或暴露于OVA + ROFA-s的相似暴露确实导致AHR，没有联合暴露增强的证据。相比之下，暴露于OVA和ROFA-s的非常年轻的小鼠显示出显著增加的AHR（例如，Penh +50 mg/ml乙酰甲胆碱用于OVA + ROFA-s对比单独的OVA = 2.6 ± 0.4 [平均值± SE]，对比1.2 ± 0.1; p < 0.01，n = 100 15），并在一周后过敏原攻击时产生OVA特异性IgE和IgG。在第11天从小鼠中取出的气道的免疫染色显示在OVA + ROFA-s暴露后Ia+细胞显著增加。我们的结论是，暴露于污染物气溶胶可以破坏正常的抵抗吸入过敏原致敏，从而可以促进发展的新生儿/幼年小鼠模型的气道超敏反应。
The role of air pollution in the initiation of asthma is controversial. We sought to model the potential effects of air pollution on immune responses to inhaled allergens in developing lungs by using very young mice. Neonatal mice were repeatedly exposed to aerosolized ovalbumin (OVA; 3% in phosphate-buffered saline for 10 min/d, from Days 5 to 15 of age). Some mice were also exposed to leachate of residual oil fly ash (ROFA-s), a surrogate for ambient air particles, for 30 min, on Days 6, 8, and 10 of age). Repeated exposure of very young mice to allergen alone (OVA) or pollutant alone (ROFA-s) had no effect on airway hyperresponsiveness (AHR, measured as enhanced pause (Penh) with noninvasive plethysmography at Day 16 of age), and did not cause inflammation or OVA-specific antibody production. Similar exposures of adult mice to either OVA alone or to OVA + ROFA-s did result in AHR, without evidence of enhancement by combined exposure. In contrast, very young mice exposed to both OVA and ROFA-s showed significantly increased AHR (e.g., Penh with 50 mg/ml methacholine for OVA + ROFA-s versus OVA alone = 2.6 ± 0.4 [mean ± SE], versus 1.2 ± 0.1; p < 0.01, n ⩾ 15), and produced OVA-specific IgE and IgG upon allergen challenge a week later. Immunostaining of airways taken from mice at Day 11 showed a marked increase in Ia+cells after OVA + ROFA-s exposure. We conclude that exposure to pollutant aerosols can disrupt normal resistance to sensitization to inhaled allergens, and can thereby promote development of airway hypersensitivity in this neonatal/juvenile mouse model.