Kumar R K, Herbert C, Kasper M
Department of Pathology, University of New South Wales, Sydney, Australia.
Clin Exp Allergy. 2004 Nov;34(11):1796-802. doi: 10.1111/j.1365-2222.2004.02097.x.
Asthma is associated with recruitment of eosinophils, accumulation of chronic inflammatory cells in the airway walls, subepithelial fibrosis and other structural changes of airway wall remodelling. The role of ongoing exposure to allergens in their pathogenesis remains unclear.
To examine whether changes of inflammation and remodelling were reversible following cessation of antigenic challenge in a mouse model of chronic asthma.
BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged by inhalation of a low mass concentration of antigen for 8 weeks, leading to development of acute-on-chronic airway inflammation, subepithelial fibrosis and other changes of airway wall remodelling. Epithelial injury was assessed by immunohistochemistry, while inflammation and remodelling were quantified by appropriate histomorphometric techniques. Regression of lesions was assessed in animals examined at 1, 2 and 4 weeks after exposure to OVA ceased.
We did not find evidence of airway epithelial injury in this model of low-level chronic inhalational exposure to antigen. Persistence of the recruitment of eosinophils and chronic inflammatory cells in the airway walls was dependent on continuing antigenic challenge, as was persistence of mucous cell hyperplasia/metaplasia. Subepithelial fibrosis and epithelial hypertrophy exhibited delayed reversibility following cessation of exposure to antigen, possibly related to matrix-associated accumulation of transforming growth factor-beta(1).
In chronic asthma, low-level antigenic challenge may be required to maintain the inflammatory response in the airway wall, but airway remodelling may persist in its absence.
哮喘与嗜酸性粒细胞募集、气道壁慢性炎症细胞积聚、上皮下纤维化以及气道壁重塑的其他结构变化有关。持续接触变应原在其发病机制中的作用仍不清楚。
在慢性哮喘小鼠模型中，研究停止抗原激发后炎症和重塑变化是否可逆。
用卵清蛋白（OVA）致敏的BALB/c小鼠通过吸入低质量浓度抗原进行8周的慢性激发，导致慢性气道炎症急性发作、上皮下纤维化及气道壁重塑的其他变化。通过免疫组织化学评估上皮损伤，同时采用适当的组织形态计量学技术对炎症和重塑进行量化。在停止接触OVA后1周、2周和4周检查的动物中评估病变的消退情况。
在这种低水平慢性吸入抗原暴露模型中，我们未发现气道上皮损伤的证据。气道壁中嗜酸性粒细胞和慢性炎症细胞募集的持续存在取决于持续的抗原激发，黏液细胞增生/化生的持续存在也是如此。停止接触抗原后，上皮下纤维化和上皮肥大表现出延迟的可逆性，这可能与转化生长因子-β(1)的基质相关积聚有关。
在慢性哮喘中，可能需要低水平的抗原激发来维持气道壁中的炎症反应，但在无抗原激发的情况下气道重塑可能持续存在。
