CHARACTERIZATION OF A MURINE MODEL OF ALLERGIC PULMONARY INFLAMMATION
CHARACTERIZATION OF A MURINE MODEL OF ALLERGIC PULMONARY INFLAMMATION
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DOI：
10.1159/000236807
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发表时间：
1994-09-01
影响因子：
2.8
通讯作者：
WATNICK, AS
中科院分区：
文献类型：
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作者：
KUNG, TT;JONES, H;WATNICK, AS
嗜酸性粒细胞（EOs）浸润的肺部炎症是过敏性呼吸系统疾病（如哮喘）的显著特征。为了研究疾病发展过程中的细胞反应，需要IgE介导的具有特征性嗜酸性粒细胞增多的肺部炎症的动物模型。我们开发了一种诱导小鼠严重肺嗜酸性粒细胞增多的方法，并研究了血液和骨髓中的EOS数量以及对皮质类固醇治疗的反应。用明矾沉淀的卵清蛋白（OVA）致敏动物，并在12天后血清IgE水平显著升高时用雾化的OVA进行攻击。激发后4 - 8小时，骨髓和外周血中的EO数量中度增加，但在肺组织和支气管肺泡灌洗（BAL）液中仅观察到少数EO。激发后24小时，骨髓中的EO显著减少，而肺血管周围和支气管周围区域的EO数量达到峰值。攻击后48小时，在BAL液中发现最高数量的EO，占该隔室中所有细胞的>80%。肺组织和支气管肺泡灌洗液中高水平的嗜酸性粒细胞持续2-3天，随后出现更中度但持续10天的嗜酸性粒细胞增多。未致敏动物的BAL液、肺、血液或骨髓中的EO数量无显著变化。组织学评价还显示上皮损伤、管腔中粘液过多和气道粘膜下层水肿。OVA激发诱导的肺嗜酸性粒细胞增多和骨髓EOS减少对几种标准皮质类固醇治疗反应良好。激素抑制肺嗜酸性粒细胞增多的作用顺序为：强的松龙>氢化可的松。由于小鼠在免疫学研究中非常有用，因此该模型对于研究细胞因子对肺部炎症的影响非常有用。
Pulmonary inflammation with eosinophil (EOs) infiltration is a prominent feature of allergic respiratory diseases such as asthma. In order to study the cellular response during the disease development, an animal model of IgE-mediated pulmonary inflammation with characteristic eosinophilia is needed. We developed a method for inducing severe pulmonary eosinophilia in the mouse and also studied the numbers of EOs in blood and bone marrow and the response to corticosteroid treatment. Animals were sensitized with alum-precipitated ovalbumin (OVA) and challenged with aerosolized OVA 12 days later when serum IgE levels were significantly elevated. Four to eight hours after challenge there were moderate increases in the number of EOs in the bone marrow and peripheral blood, but only a few EOs were observed in the lung tissue and in bronchoalveolar lavage (BAL) fluid. Twenty-four hours after challenge, there was a marked reduction of EOs in bone marrow while the number of EOs peaked in the perivascular and peribronchial regions of the lung. Forty-eight hours after challenge, the highest number of EOs was found in the BAL fluid, making up >80% of all cells in that compartment. The high levels of EOs in the lung tissue and BAL fluid lasted for 2-3 days and was followed by a more moderate but persistent eosinophilia for another 10 days. Nonsensitized animals showed no significant changes in the number of EOs in BAL fluid, lungs, blood or bone marrow. Histopathological evaluation also revealed epithelial damage, excessive mucus in the lumen and edema in the submucosa of the airways. The pulmonary eosinophilia and decrease in bone marrow EOs induced by OVA challenge responded well to treatment with several standard corticosteroids. The rank order of steroid potency for inhibition of pulmonary eosinophilia was betamethasone > prednisolone > hydrocortisone. Because mice are extremely useful for immunological studies, this model can be invaluable to study the effects of cytokines on pulmonary inflammation.