Hubbard Andrea K, Symanowicz Peter T, Thibodeau Michael, Thrall Roger S, Schramm Craig M, Cloutier Michelle M, Morris John B
Department of Pharmaceutical Sciences, University of Connecticut, Storrs 06269, USA.
J Toxicol Environ Health A. 2002 Dec 13;65(23):1999-2005. doi: 10.1080/00984100290071397.
The effect of exposure to irritant air pollutants on the development of allergic airway disease is poorly understood. This study examines the effects of the lower respiratory tract irritant, NO(2), on the outcome of ovalbumin (OVA)-induced allergic airway disease. Male and female C57Bl/6 mice were sensitized by weekly intraperitoneal (ip) OVA injections for 3 wk followed by daily 1-h OVA aerosol inhalation challenge for 3 or 10 d. Initially, mice were exposed daily for 3 d to air or 0.7 or 5 ppm NO(2) for 2 h following each OVA aerosol challenge. OVA exposure resulted in pronounced lower airway inflammation, as evidenced by a significant increase in bronchoalveolar lavage (BAL) total cellularity and eosinophil levels. BAL eosinophil levels were significantly lower in OVA-NO(2) compared to OVA-air animals. The reduction was similar at both NO(2) exposure concentrations. In a subsequent study, sensitized animals were exposed for 3 or 10 d to aerosolized OVA followed by air or 0.7 ppm NO(2). BAL eosinophils were again reduced at 3 d by OVA-NO(2) exposure compared to OVA-air mice. At 10 d the eosinophilia was virtually abolished. This reduction in OVA-induced cellular inflammation by NO(2) was confirmed by histopathological analysis. Contrary to expectations, exposure to NO(2) during the aerosol challenge to OVA dramatically diminished the outcome of allergic disease in lungs as measured by airway cellular inflammation.
暴露于刺激性空气污染物对过敏性气道疾病发展的影响尚不清楚。本研究考察了下呼吸道刺激物二氧化氮(NO₂)对卵清蛋白(OVA)诱导的过敏性气道疾病结局的影响。对雄性和雌性C57Bl/6小鼠每周腹腔注射OVA,连续3周进行致敏,随后每天进行1小时的OVA雾化吸入激发,持续3天或10天。最初,在每次OVA雾化激发后,小鼠每天暴露于空气或0.7或5 ppm的NO₂中2小时,持续3天。OVA暴露导致明显的下呼吸道炎症,支气管肺泡灌洗(BAL)总细胞数和嗜酸性粒细胞水平显著增加证明了这一点。与OVA-空气组动物相比,OVA-NO₂组BAL嗜酸性粒细胞水平显著降低。在两个NO₂暴露浓度下,这种降低情况相似。在随后的研究中,致敏动物暴露于雾化OVA 3天或10天,随后暴露于空气或0.7 ppm的NO₂中。与OVA-空气组小鼠相比,OVA-NO₂暴露在3天时再次降低了BAL嗜酸性粒细胞水平。在10天时,嗜酸性粒细胞增多症几乎消失。组织病理学分析证实了NO₂对OVA诱导的细胞炎症的这种降低作用。与预期相反,在OVA雾化激发期间暴露于NO₂显著减轻了以气道细胞炎症衡量的肺部过敏性疾病的结局。