Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice1
Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice1
复制标题
显着的气道嗜酸性粒细胞增多可防止 IL-5 转基因小鼠过敏反应期间气道高反应性的发展1
作者：
Takao Kobayashi;K. Iijima;H. Kita
组织嗜酸性粒细胞增多可能在支气管哮喘和变应性疾病的病理生理中起重要作用；然而，最近在小鼠支气管哮喘模型中使用抗il -5抗体治疗的结果和人类抗il -5治疗的失败，这一概念受到了挑战。我们现在使用一种独特的模型，IL-5转基因（TG）小鼠，来解决一个基本问题：气道嗜酸性粒细胞在过敏反应中是有益的还是有害的？在致敏和OVA刺激后，IL-5 TG小鼠表现出明显的气道嗜酸性粒细胞增多。令人惊讶的是，这些IL-5 TG小鼠对甲胆碱的气道反应性较低。肺免疫组化分析显示支气管周围有明显的嗜酸性粒细胞浸润，但未见嗜酸性粒细胞脱粒。在体外，小鼠腹膜灌洗液中的嗜酸性粒细胞不产生超氧阴离子，但产生抗炎和纤维化细胞因子TGF-β1。IL-5 TG小鼠支气管肺泡灌洗液标本中TGF-β1水平与气道嗜酸性直接相关（r = 0.755）。此外，IL-5 TG小鼠抗IL-5处理降低了支气管肺泡灌洗液中嗜酸性粒细胞和TGF-β1水平，增加了气道反应性。因此，在小鼠中，明显的嗜酸性粒细胞阻止了过敏反应期间气道高反应性的发展。总的来说，嗜酸性粒细胞在哮喘和动物模型中的作用需要仔细处理，因为它们可能具有有害和有益的作用。
Tissue eosinophilia probably plays important roles in the pathophysiology of bronchial asthma and allergic disorders; however, this concept was challenged recently by controversial results in mouse models of bronchial asthma treated with anti-IL-5 Ab and the failure of anti-IL-5 therapy in humans. We have now used a unique model, IL-5 transgenic (TG) mice, to address a fundamental question: is airway eosinophilia beneficial or detrimental in the allergic response? After sensitization and challenge with OVA, IL-5 TG mice showed a marked airway eosinophilia. Surprisingly, these IL-5 TG mice showed lower airway reactivity to methacholine. Immunohistochemical analysis of the lungs revealed a marked peribronchial infiltration of eosinophils, but no eosinophil degranulation. In vitro, mouse eosinophils from peritoneal lavage fluids did not produce superoxide anion, but did produce an anti-inflammatory and fibrotic cytokine, TGF-β1. Indeed, the TGF-β1 levels in bronchoalveolar lavage fluid specimens from IL-5 TG mice directly correlated with airway eosinophilia (r = 0.755). Furthermore, anti-IL-5 treatment of IL-5 TG mice decreased both airway eosinophilia and TGF-β1 levels in bronchoalveolar lavage fluids and increased airway reactivity. Thus, in mice, marked eosinophilia prevents the development of airway hyper-reactivity during an allergic response. Overall, the roles of eosinophils in asthma and in animal models need to be addressed carefully for their potentially detrimental and beneficial effects.
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DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
24.7
作者：
Hamelmann, E;Schwarze, J;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
--
作者：
G. Gleich;C. Adolphson
通讯作者：
G. Gleich;C. Adolphson
影响因子：
15.9
作者：
Shi, HZ;Humbles, A;Weller, PF
通讯作者：
Weller, PF
Fc gamma RII (CD32) 的连接对人类嗜酸性粒细胞的存活起着关键性调节作用。
DOI：
--
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim,JT;Schimming,AW;Kita,H
通讯作者：
Kita,H
β2 整合素在 IgG 刺激的嗜酸性粒细胞活化中发挥着至关重要的作用。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaneko,M;Horie,S;Kato,M;Gleich,GJ;Kita,H
通讯作者：
Kita,H