Djukanović R, Feather I, Gratziou C, Walls A, Peroni D, Bradding P, Judd M, Howarth P H, Holgate S T
Immunopharmacology Group, University Medicine, Southampton, UK.
Thorax. 1996 Jun;51(6):575-81. doi: 10.1136/thx.51.6.575.
Bronchial challenge with allergen causes a specific form of airways inflammation consisting of an influx of neutrophils, eosinophils, and T cells. Because the relevance of the challenge model to clinical asthma is uncertain, the cellular changes that occur in the lungs of asthmatic subjects during natural seasonal allergen exposure were investigated.
Seventeen grass pollen sensitive asthmatic subjects with previously reported seasonal exacerbations of asthma kept records of symptoms and underwent fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy before and during the peak of the grass pollen season. The BAL cells were analysed for differential cell counts and by flow cytometry for T cell subsets and surface activation markers. The biopsy samples were processed into glycol methacrylate resin and immunohistochemical analysis was performed for mast cells, activated eosinophils, T cells and interleukin 4 (IL-4), a cytokine with a pivotal role in allergen-induced inflammation.
In the pollen season there was an increase in T lymphocyte activation in the BAL fluid as identified by increased expression of interleukin 2 receptor (IL-2R). In the submucosa these changes were paralleled by an increase in CD4+ T cells. By contrast, the numbers of metachromatic cells in BAL fluid staining with toluidine blue were reduced, possibly because of degranulation following allergen stimulation. In keeping with mast cell activation, the number of mucosal mast cells staining for secreted IL-4 increased during the season. In comparison with the period shortly before the onset of the season, all but two subjects experienced an asthma exacerbation which followed the rise in pollen counts but, compared with the period preceding the first bronchoscopic examination, asthma symptoms were not increased during the pollen season.
The data suggest that natural allergen exposure, leading to a clinical exacerbation of asthma, may induce an inflammatory response involving T cells, mast cells and eosinophils. The relationship between allergen exposure, cellular infiltration and activation, and clinical symptoms appears to be complex, with factors other than allergen also contributing to asthmatic activity.
用变应原进行支气管激发会引发一种特定形式的气道炎症,包括中性粒细胞、嗜酸性粒细胞和T细胞的流入。由于激发模型与临床哮喘的相关性尚不确定,因此对哮喘患者在自然季节性变应原暴露期间肺部发生的细胞变化进行了研究。
17名对草花粉敏感且先前有季节性哮喘加重报告的哮喘患者记录症状,并在草花粉季节高峰期之前和期间接受纤维支气管镜检查及支气管肺泡灌洗(BAL)和支气管内活检。对BAL细胞进行细胞分类计数分析,并通过流式细胞术分析T细胞亚群和表面活化标志物。将活检样本处理成乙二醇甲基丙烯酸酯树脂,并对肥大细胞、活化嗜酸性粒细胞、T细胞和白细胞介素4(IL-4,一种在变应原诱导的炎症中起关键作用的细胞因子)进行免疫组织化学分析。
在花粉季节,BAL液中T淋巴细胞活化增加,表现为白细胞介素2受体(IL-2R)表达增加。在黏膜下层,这些变化与CD4+T细胞增加同时出现。相比之下,用甲苯胺蓝染色的BAL液中异染细胞数量减少,可能是由于变应原刺激后脱颗粒所致。与肥大细胞活化一致,分泌IL-4染色的黏膜肥大细胞数量在季节期间增加。与季节开始前不久相比,除两名患者外,所有患者均经历了哮喘加重,且哮喘加重与花粉计数上升相关,但与首次支气管镜检查前相比,花粉季节期间哮喘症状并未增加。
数据表明,导致哮喘临床加重 的自然变应原暴露可能诱导涉及T细胞、肥大细胞和嗜酸性粒细胞的炎症反应。变应原暴露、细胞浸润和活化与临床症状之间的关系似乎很复杂,除变应原外的其他因素也会影响哮喘活动。