Yasruel Z, Humbert M, Kotsimbos T C, Ploysongsang Y, Minshall E, Durham S R, Pfister R, Menz G, Tavernier J, Kay A B, Hamid Q
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Am J Respir Crit Care Med. 1997 Apr;155(4):1413-8. doi: 10.1164/ajrccm.155.4.9105087.
Eosinophilic inflammation and interleukin-5 (IL-5) expression are characteristic features of the bronchial mucosa in asthma. We have investigated the differential expression of membrane and soluble isoforms of alpha IL-5 receptor (alpha IL-5Rm and alpha IL-5Rs) mRNA in asthmatics and in normal control subjects and examined the correlation between alpha IL-5Rm and alpha IL-5Rs expression and the FEV1 and airway hyperresponsiveness. Nineteen subjects with stable asthma (atopic = 9; intrinsic = 10) and 22 control subjects (atopic = 12; nonatopic = 10) were recruited. Endobronchial biopsies were obtained and processed for in situ hybridization and double-staining techniques. There was a significant increase in the number of cells per millimeter basement membrane expressing mRNA for total, membrane-bound, and soluble alpha IL-5R in asthmatics when compared with that in nonasthmatic control subjects (p < 0.001); 93% of the cells positive for alpha IL-5R mRNA were EG2+ve eosinophils. There was no significant difference in the expression of alpha IL-5Rm and alpha IL-5Rs between the atopic and nonatopic asthmatics. The expression of alpha IL-5Rm and alpha IL-5Rs was also nonsignificantly different between the atopic and nonatopic control subjects. However, in the asthmatic subjects, the number of positive cells expressing mRNA for alpha IL-5Rm inversely correlated with FEV1(r2 = 0.89, p < 0.001), whereas the expression of alpha IL-5Rs mRNA directly correlated with FEV1 (r2 = 0.52, p < 0.001). There were no significant correlations between alpha IL-5R isoforms and the methacholine PC20. These results suggest that alpha IL-5R upregulation and differential regulation of alternatively spliced alpha IL-5R mRNA transcripts may influence the eosinophil response and the accompanying changes in airflow limitation in both atopic and nonatopic variants of chronic asthma.
嗜酸性粒细胞炎症和白细胞介素-5（IL-5）表达是哮喘患者支气管黏膜的特征性表现。我们研究了哮喘患者和正常对照者中α白细胞介素-5受体（αIL-5Rm和αIL-5Rs）mRNA的膜结合型和可溶性亚型的差异表达，并检测了αIL-5Rm和αIL-5Rs表达与第一秒用力呼气容积（FEV1）及气道高反应性之间的相关性。招募了19例稳定期哮喘患者（特应性哮喘9例；非特应性哮喘10例）和22例对照者（特应性12例；非特应性10例）。获取支气管活检组织并进行原位杂交和双重染色技术处理。与非哮喘对照者相比，哮喘患者每毫米基底膜上表达总αIL-5R、膜结合型αIL-5R和可溶性αIL-5R mRNA的细胞数量显著增加（p < 0.001）；αIL-5R mRNA阳性细胞中93%为EG2+嗜酸性粒细胞。特应性哮喘患者和非特应性哮喘患者之间αIL-5Rm和αIL-5Rs的表达无显著差异。特应性对照者和非特应性对照者之间αIL-5Rm和αIL-5Rs的表达也无显著差异。然而，在哮喘患者中，表达αIL-5Rm mRNA的阳性细胞数量与FEV1呈负相关（r2 = 0.89，p < 0.001），而αIL-5Rs mRNA的表达与FEV1呈正相关（r2 = 0.52，p < 0.001）。αIL-5R亚型与乙酰甲胆碱PC20之间无显著相关性。这些结果表明，αIL-5R上调以及选择性剪接的αIL-5R mRNA转录本的差异调节可能会影响嗜酸性粒细胞反应以及慢性哮喘特应性和非特应性变体中伴随的气流受限变化。
