Oxidant stress modulates murine allergic airway responses.
Oxidant stress modulates murine allergic airway responses.
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DOI：
10.1016/j.freeradbiomed.2005.11.012
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发表时间：
2006-04
影响因子：
7.4
通讯作者：
Meghavi Talati;B. Meyrick;R. Peebles;S. Davies;R. Dworski;R. Mernaugh;D. Mitchell;M. Boothby;L. Roberts;J. Sheller
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文献类型：
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作者：
Meghavi Talati;B. Meyrick;R. Peebles;S. Davies;R. Dworski;R. Mernaugh;D. Mitchell;M. Boothby;L. Roberts;J. Sheller
哮喘中发生的过敏性炎症被认为伴随着自由基的产生。为了研究自由基的作用和受影响的细胞，我们转向致敏卵白蛋白与随后的气溶胶挑战产生的过敏性炎症的小鼠模型。我们通过测量和定位脂质过氧化的敏感和特异性标志物F2-异前列腺素来检查氧化应激。全肺中的F2-异前列烷从基线时的0.30 ± 0.08 ng/肺增加至每日气雾剂变应原激发第9天的峰值0.061 ± 0.09 ng/肺。首次气溶胶激发后24小时，在上皮细胞中发现15-F2 t-IsoP（8-iso-PGF 2 α）或异缩酮蛋白加合物的免疫反应性增加，第5天在巨噬细胞中发现。胶原蛋白周围的气道和血管，气道和血管平滑肌，也表现出增加免疫反应后，卵清蛋白的挑战。饮食维生素E限制与过敏性炎症导致增加全肺F2-异前列腺素，而补充维生素E抑制其形成。观察到与F2-异前列腺素免疫反应性的相似变化。气道对乙酰甲胆碱的反应性也因维生素E缺乏而增加，补充抗氧化剂后略有下降。我们的研究结果表明，小鼠过敏性气道炎症与氧化应激的增加有关，这在气道上皮细胞和巨噬细胞中最为显著。氧化应激在气道反应性的产生中起作用。
The allergic inflammation occurring in asthma is believed to be accompanied by the production of free radicals. To investigate the role of free radicals and the cells affected we turned to a murine model of allergic inflammation produced by sensitization to ovalbumin with subsequent aerosol challenge. We examined oxidant stress by measuring and localizing the sensitive and specific marker of lipid peroxidation, the F2-isoprostanes. F2-isoprostanes in whole lung increased from 0.30 ± 0.08 ng/lung at baseline to a peak of 0.061 ± 0.09 ng/lung on the ninth day of daily aerosol allergen challenge. Increased immunoreactivity to 15-F2t-IsoP (8-iso-PGF2α) or to isoketal protein adducts was found in epithelial cells 24 h after the first aerosol challenge and at 5 days in macrophages. Collagen surrounding airways and blood vessels, and airway and vascular smooth muscle, also exhibited increased immunoreactivity after ovalbumin challenge. Dietary vitamin E restriction in conjunction with allergic inflammation led to increased whole lung F2-isoprostanes while supplemental vitamin E suppressed their formation. Similar changes in immunoreactivity to F2-isoprostanes were seen. Airway responsiveness to methacholine was also increased by vitamin E depletion and decreased slightly by supplementation with the antioxidant. Our findings indicate that allergic airway inflammation in mice is associated with an increase in oxidant stress, which is most striking in airway epithelial cells and macrophages. Oxidant stress plays a role in the production of airway responsiveness.