Lapa e Silva J R, Bachelet C M, Pretolani M, Baker D, Scheper R J, Vargaftig B B
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM no. 285, Paris, France.
Am J Respir Cell Mol Biol. 1993 Jul;9(1):44-53. doi: 10.1165/ajrcmb/9.1.44.
Isolated lungs from guinea pigs actively sensitized to ovalbumin and boosted 2 wk later display an enhanced bronchoconstriction and release larger amounts of secondary mediators as compared with lungs from nonimmunized animals when stimulated by platelet-activating factor or other agonists. We have investigated changes in T lymphocytes and eosinophils found in the bronchial wall of immunized and nonimmunized guinea pigs. The animals received two injections of 10 micrograms ovalbumin in Al(OH)3, at a 2-wk interval. Two studies were performed: (1) the animals were killed 7 days after the booster injection of antigen, (2) they were challenged with ovalbumin at this same day and killed after 2 or 24 h. Lungs were resected and frozen, and cryostat sections stained using monoclonal antibodies that recognize T cells, T cell subsets, or other relevant epitopes. Cyanide-resistant peroxidase activity was used to identify eosinophils. A large number of T cells, mainly of the CD4+ subset, and eosinophils were recruited into the bronchi 7 days after the booster injection of the antigen, compared with nonimmunized or nonboosted animals. In antigen-challenged animals, the numbers of T cells did not change but eosinophils were further increased in number at the 24 h time point. Also at this time point, a population of cells with a dendritic appearance was seen in the bronchial wall, which did not express macrophage markers but was strongly class II positive. Class II positivity was also noted in the bronchial epithelium and on many cells infiltrating the mucosa. These findings suggest that activated T cells and/or their products play an important role in the bronchopulmonary immunopathology associated with this model and possibly with the development of bronchial hyperreactivity.
与未免疫动物的肺相比,用卵清蛋白主动致敏并在2周后加强免疫的豚鼠离体肺,在受到血小板活化因子或其他激动剂刺激时,会表现出增强的支气管收缩,并释放更多的次级介质。我们研究了免疫和未免疫豚鼠支气管壁中T淋巴细胞和嗜酸性粒细胞的变化。动物每隔2周接受两次10微克卵清蛋白与氢氧化铝的注射。进行了两项研究:(1)在加强注射抗原7天后处死动物;(2)在同一天用卵清蛋白攻击动物,并在2或24小时后处死。切除肺并冷冻,用识别T细胞、T细胞亚群或其他相关表位的单克隆抗体对冰冻切片进行染色。用抗氰过氧化物酶活性来鉴定嗜酸性粒细胞。与未免疫或未加强免疫的动物相比,在加强注射抗原7天后,大量T细胞(主要是CD4 +亚群)和嗜酸性粒细胞被募集到支气管中。在抗原攻击的动物中,T细胞数量没有变化,但在24小时时间点嗜酸性粒细胞数量进一步增加。同样在这个时间点,在支气管壁中可见一群具有树突状外观的细胞,它们不表达巨噬细胞标志物,但II类分子呈强阳性。在支气管上皮和许多浸润黏膜的细胞上也观察到II类分子阳性。这些发现表明,活化的T细胞和/或其产物在与该模型相关的支气管肺免疫病理学以及可能与支气管高反应性的发展中起重要作用。