Shvedova A A, Kisin E R, Kagan V E, Karol M H
Department of Environmental and Occupational Health, University of Pittsburgh 15238, USA.
Toxicol Appl Pharmacol. 1995 May;132(1):72-81. doi: 10.1006/taap.1995.1088.
Oxygen-derived radicals and cytokines are known to play key roles in cellular inflammation accompanying allergic lung disease. Using a well-characterized guinea pig model of pulmonary ovalbumin (OA) hypersensitivity, we studied lipid peroxidation and endogenous antioxidant reserve in bronchoalveolar lung fluid (BAL) following a severe pulmonary allergic reaction. Since TNF-alpha is known to be involved in oxygen radical generation, we also examined TNF production in response to antigen challenge. By 24 hr after antigen challenge, the number of eosinophils in BAL was increased 3.5-fold compared with nonsensitized but challenged control animals. Immunohistochemical evaluation of BAL cells, employing a polyclonal antibody to murine TNF-alpha, demonstrated the presence of TNF in eosinophils. A 2.4-fold higher concentration of lipid peroxidation products was found in BAL fluid of sensitized and challenged vs nonsensitized, challenged guinea pigs (p < 0.05). Endogenous antioxidant levels were lower in the BAL fluid of the sensitized, challenged guinea pigs. The concentration of the major lipid-soluble antioxidant, vitamin E, was 8.7-fold lower than that in nonsensitized controls (p < 0.001) and the endogenous reserve of water-soluble antioxidants (thiols and ascorbic acid) was decreased 4-fold from that of control animals (p < 0.02). These results indicate an antioxidant/prooxidant imbalance associated with an allergic pulmonary episode.
氧衍生自由基和细胞因子在过敏性肺病伴随的细胞炎症中发挥关键作用。利用一种特征明确的豚鼠卵清蛋白（OA）肺部过敏模型，我们研究了严重肺部过敏反应后支气管肺泡灌洗液（BAL）中的脂质过氧化和内源性抗氧化储备。由于已知肿瘤坏死因子-α（TNF-α）参与氧自由基的产生，我们还检测了抗原激发后TNF的产生。抗原激发后24小时，与未致敏但激发的对照动物相比，BAL中嗜酸性粒细胞数量增加了3.5倍。用抗小鼠TNF-α的多克隆抗体对BAL细胞进行免疫组织化学评估，结果显示嗜酸性粒细胞中存在TNF。与未致敏、激发的豚鼠相比，致敏并激发的豚鼠BAL液中脂质过氧化产物浓度高2.4倍（p<0.05）。致敏、激发的豚鼠BAL液中的内源性抗氧化水平较低。主要脂溶性抗氧化剂维生素E的浓度比未致敏对照低8.7倍（p<0.001），水溶性抗氧化剂（硫醇和抗坏血酸）的内源性储备比对照动物减少了4倍（p<0.02）。这些结果表明抗氧化剂/促氧化剂失衡与过敏性肺部发作有关。
