Skripuletz Thomas, Schmiedl Andreas, Schade Jutta, Bedoui Sammy, Glaab Thomas, Pabst Reinhard, von Hörsten Stephan, Stephan Michael
Department of Functional and Applied Anatomy, Medical School of Hannover, Germany.
Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1564-71. doi: 10.1152/ajplung.00273.2006. Epub 2007 Mar 9.
The ovalbumin (OVA)-induced airway inflammation in rats is a commonly used model to explore the pathobiology of asthma. However, its susceptibility varies greatly between rat strains, and presently Brown Norway (BN) rats are preferentially used. Since recruitment of T cells to the lungs depends on the CD26 (dipeptidyl peptidase IV, DPPIV) expression, Fischer 344 strain (F344) rats are a highly relevant rat strain, in particular because CD26-deficient substrains are available. To establish a F344 rat model of asthma, we challenged F344 rats using different doses of aerosolized antigen (0%, 1%, 2.5%, 5%, and 7.5% OVA) and compared these effects with intratracheal instillation of OVA (1.5 mg/0.3 ml). Asthmoid responsiveness was determined by analysis of early airway responsiveness (EAR), antigen-specific IgE levels, as well as airway inflammation including the composition of T cell subpopulations in the bronchoalveolar lavage (BAL) and lung tissue with special respect to the T cell activation markers CD25 and CD26. Even low allergen doses caused allergen-specific EAR and increases of antigen-specific IgE levels. However, EAR and IgE levels did not increase dose dependently. Higher concentrations of OVA led to a dose-dependent increase of several immunological markers of allergic asthma including an influx of eosinophils, T cells, and dendritic cells. Interestingly, a dose-dependent increase of CD4(+)/CD25(+)/CD26(+) T cells was found in the lungs. Summarizing, we established a novel F344 rat model of aerosolized OVA-induced asthma. Thereby, we found a dose-dependent recruitment of cellular markers of allergic asthma including the activated CD4(+)/CD25(+)/CD26(+) T cell subpopulation, which has not been described in asthma yet.
卵清蛋白（OVA）诱导的大鼠气道炎症是探索哮喘病理生物学常用的模型。然而，不同大鼠品系对其易感性差异很大，目前优先选用的是挪威棕（BN）大鼠。由于T细胞向肺内的募集依赖于CD26（二肽基肽酶IV，DPPIV）的表达，Fischer 344品系（F344）大鼠是一种高度相关的大鼠品系，特别是因为有CD26缺陷的亚品系。为建立F344大鼠哮喘模型，我们用不同剂量的雾化抗原（0%、1%、2.5%、5%和7.5% OVA）对F344大鼠进行激发，并将这些效应与气管内注入OVA（1.5 mg/0.3 ml）进行比较。通过分析早期气道反应性（EAR）、抗原特异性IgE水平以及气道炎症（包括支气管肺泡灌洗（BAL）和肺组织中T细胞亚群的组成，特别关注T细胞活化标志物CD25和CD26）来确定哮喘样反应性。即使是低剂量变应原也会引起变应原特异性EAR并增加抗原特异性IgE水平。然而，EAR和IgE水平并非呈剂量依赖性增加。较高浓度的OVA导致过敏性哮喘的几种免疫标志物呈剂量依赖性增加，包括嗜酸性粒细胞、T细胞和树突状细胞的流入。有趣的是，在肺中发现CD4(+)/CD25(+)/CD26(+) T细胞呈剂量依赖性增加。总之，我们建立了一种新型的雾化OVA诱导的F344大鼠哮喘模型。由此，我们发现了过敏性哮喘细胞标志物的剂量依赖性募集，包括活化的CD4(+)/CD25(+)/CD26(+) T细胞亚群，这在哮喘中尚未见报道。
