Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice
Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice
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DOI：
10.1172/jci118560
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发表时间：
1996-03-15
影响因子：
15.9
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Oshiba, A;Hamelmann, E;Gelfand, EW
在一部分特应性哮喘患者中，接触相关抗原后会出现气道慢性炎症，导致气道反应性（AR）改变。然而，气道高反应性发展的机制仍不清楚。为了阐明 IgE 介导的反应与气道高反应性之间的关系，使用来自小鼠 B 细胞杂交瘤的抗 OVA IgE 和 IgG 抗体开发了被动致敏和卵清蛋白 (OVA) 气道激发的小鼠模型。静脉注射抗 OVA IgE 被动致敏导致立即皮肤过敏，连续两天用 OVA 进行气道激发后，BALB/c 和 SJL 小鼠的 AR 增加。与未致敏的小鼠相比，被动用 IgE 致敏并通过气道攻击的 BALB/c 小鼠的支气管肺泡灌洗液、从肺部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，抗 OVA IgG1（而非 IgG2a 或 IgG3）的被动致敏同样与皮试反应性的发展和气道激发后 AR 增加相关，同时伴有支气管肺泡灌洗液中嗜酸性粒细胞的增加。这些数据表明，IgE/IgG1 介导的反应以及抗原的局部攻击可导致过敏性炎症，从而改变气道功能。
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.