Temelkovski J, Hogan S P, Shepherd D P, Foster P S, Kumar R K
Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.
Thorax. 1998 Oct;53(10):849-56. doi: 10.1136/thx.53.10.849.
Existing murine models of asthma lack many of the inflammatory and epithelial changes that are typical of the human disease. Moreover, these models are frequently complicated by allergic alveolitis.
High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentrations of aerosolised ovalbumin. Titres of antiovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulation of inflammatory cells and histopathological abnormalities of the epithelium were quantified morphometrically in the trachea and the lungs, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine.
Mice sensitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low concentrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characterised by the presence of intraepithelial eosinophils and by infiltration of the lamina propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithelial fibrosis were evident following chronic exposure. In parallel, the mice developed increased sensitivity to induction of bronchospasm, as well as increased maximal reactivity. Non-immunised mice exposed to aerosolised ovalbumin had low or absent antiovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hyperreactivity.
This experimental model replicates many of the features of human asthma and should facilitate studies of pathogenetic mechanisms and of potential therapeutic agents.
现有的哮喘小鼠模型缺乏许多人类疾病典型的炎症和上皮变化。此外，这些模型常因过敏性肺泡炎而变得复杂。
高IgE反应性BALB/c小鼠经全身致敏于卵清蛋白，并长期用低颗粒质量浓度的雾化卵清蛋白进行激发。每隔两周通过酶免疫测定法测量血清中抗卵清蛋白IgE的滴度，通过形态计量学方法对气管和肺中的炎症细胞积聚和上皮组织病理学异常进行定量，并通过静脉注射乙酰甲胆碱后测量支气管收缩来评估气道反应性。
经两次腹腔注射卵清蛋白致敏的小鼠产生了高滴度的抗卵清蛋白IgE抗体。在暴露于低浓度雾化抗原长达八周后，这些动物在气道中出现了进行性炎症反应，其特征为上皮内嗜酸性粒细胞的存在以及固有层被淋巴样/单核细胞浸润，且无相关的肺泡炎。肺内气道诱导了杯状细胞增生/化生，而长期暴露后上皮增厚和上皮下纤维化明显。同时，小鼠对支气管痉挛诱导的敏感性增加，最大反应性也增加。暴露于雾化卵清蛋白的未免疫小鼠抗卵清蛋白IgE水平低或无，未表现出炎症或上皮变化，但出现了气道高反应性。
该实验模型复制了人类哮喘的许多特征，应有助于发病机制和潜在治疗药物的研究。
