Airway inflammation in a murine model of chronic asthma: evidence for a local humoral immune response

Airway inflammation in a murine model of chronic asthma: evidence for a local humoral immune response
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DOI:
10.1046/j.1365-2222.2000.00911.x
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发表时间:
2000-10-01
影响因子:
6.1
通讯作者:
Hunter, N
Hunter, N
中科院分区:
医学2区
文献类型:
--
作者:
Kumar, RK;Temelkovski, J;Hunter, N

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背景哮喘是一种急慢性呼吸道炎症性疾病,其特征是嗜酸性粒细胞聚集到上皮层,固有层慢性炎症,以及气道壁肥大细胞的不同聚集。过敏原特异性免疫球蛋白的局部产生在触发肥大细胞介导的哮喘炎症中的作用尚不清楚。方法采用卵蛋白致敏的BALB/c小鼠慢性吸入性哮喘模型,检测气道壁免疫球蛋白分泌细胞和肥大细胞的表型。结果雾化卵白蛋白染毒6周后,致敏小鼠血浆中的慢性炎症细胞聚集体以浆细胞样细胞为主,其中包括大量的免疫球蛋白合成细胞,与对照组相比差异有统计学意义。免疫球蛋白合成细胞也存在,但在致敏暴露的小鼠中并未增加。浆细胞胞浆中的免疫球蛋白被证明是抗原特异性的。虽然血浆总IgE水平显著升高,但未观察到IgM或IgE合成细胞。结论在慢性哮喘模型中,气道壁的炎症模式与局部免疫球蛋白G介导的体液免疫反应的发展相一致。然而,没有证据表明局部产生了IgE或招募了肥大细胞。
Background Asthma is an acute-on-chronic inflammatory disease of the airways characterized by recruitment of eosinophils into the epithelial layer, chronic inflammation in the lamina propria, as well as variable accumulation of mast cells in the airway wall. The role of local production of allergen-specific immunoglobulins in triggering mast cell-mediated asthmatic inflammation is unknown.Methods We used a chronic inhalational exposure model of asthma in ovalbumin-sensitized BALB/c mice to examine the phenotype of immunoglobulin-secreting cells and mast cells in the airway wall. In parallel, we assayed ovalbumin-specific IgG and total IgE in the plasma of these animals.Results In sensitized mice exposed to aerosolized ovalbumin for 6 weeks, aggregates of chronic inflammatory cells consisted of a majority of plasmacytoid cells, including numerous IgG-synthesizing cells, which were significantly increased in sensitized animals compared to controls. IgA-synthesizing cells were also present, but were not increased in the sensitized exposed mice. Immunoglobulins in the cytoplasm of the plasma cells were demonstrated to be antigen-specific. No IgM-or IgE-synthesizing cells were observed, although levels of total IgE in the plasma were significantly increased. There was no recruitment of mast cells of either the mucosal or the connective tissue phenotype into the lamina propria or the epithelium.Conclusion In this experimental model of chronic asthma, the pattern of inflammation in the airway wall is consistent with development of a local IgG-mediated humoral immune response. However, there is no evidence of local production of IgE or recruitment of mast cells.