Oshiba A, Hamelmann E, Takeda K, Bradley K L, Loader J E, Larsen G L, Gelfand E W
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
J Clin Invest. 1996 Mar 15;97(6):1398-408. doi: 10.1172/JCI118560.
In a proportion of atopic asthmatics, exposure to a relevant antigen is followed by chronic inflammation in the airways leading to altered airway responsiveness (AR). However, the mechanisms underlying the development of airway hyperresponsiveness still remain unclear. To elucidate the relationship between IgE-mediated reactions and airway hyperresponsiveness, a murine model of passive sensitization and airway challenge with ovalbumin (OVA) was developed using anti-OVA IgE and IgG antibodies from murine B cell hybridomas. Passive sensitization by intravenous injection of anti-OVA IgE resulted in immediate cutaneous hypersensitivity and, after airway challenge with OVA on two consecutive days, increased AR in BALB/c and SJL mice. Increased numbers of eosinophils were observed in bronchoalveolar lavage fluid, in cells extracted from the lungs, and in the peribronchial areas of BALB/c mice passively sensitized with IgE and challenged through the airways compared with nonsensitized mice. Eosinophil peroxidase activity was also elevated in lung tissue from these mice. Passive sensitization with anti-OVA IgG1 but not IgG2a or IgG3 was similarly associated with development of skin test reactivity and increased AR after airway challenge, accompanied by an increase in eosinophils in bronchoalveolar lavage fluid. These data suggest that IgE/IgG1-mediated reactions together with local challenge with antigen can result in allergic inflammation resulting in altered airway function.
在一部分特应性哮喘患者中，接触相关抗原后会引发气道慢性炎症，进而导致气道反应性（AR）改变。然而，气道高反应性发展的潜在机制仍不清楚。为了阐明IgE介导的反应与气道高反应性之间的关系，利用来自小鼠B细胞杂交瘤的抗卵清蛋白（OVA）IgE和IgG抗体，建立了被动致敏和OVA气道激发的小鼠模型。静脉注射抗OVA IgE进行被动致敏会导致即刻皮肤超敏反应，在连续两天用OVA进行气道激发后，BALB/c和SJL小鼠的气道反应性增加。与未致敏小鼠相比，在经IgE被动致敏并通过气道激发的BALB/c小鼠的支气管肺泡灌洗液、从肺中提取的细胞以及支气管周围区域中，观察到嗜酸性粒细胞数量增加。这些小鼠肺组织中的嗜酸性粒细胞过氧化物酶活性也升高。用抗OVA IgG1而非IgG2a或IgG3进行被动致敏同样与皮肤试验反应性的发展以及气道激发后气道反应性增加有关，同时支气管肺泡灌洗液中的嗜酸性粒细胞增加。这些数据表明，IgE/IgG1介导的反应以及抗原局部激发可导致过敏性炎症，从而引起气道功能改变。
