MEMBRANE-BOUND AND SOLUBLE ALPHA-IL-5 RECEPTOR MESSENGER-RNA IN THE BRONCHIAL-MUCOSA OF ATOPIC AND NONATOPIC ASTHMATICS

Eosinophilic inflammation and interleukin-5 (IL-5) expression are char acteristic features of the bronchial mucosa in asthma. We have investi gated 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 a lpha IL-5Rm and alpha IL-5Rs expression and the FEV(1) and airway hype rresponsiveness. Nineteen subjects with stable asthma (atopic = 9; int rinsic = 10) and 22 control subjects (atopic = 12; nonatopic = 10) wer e recruited. Endobronchial biopsies were obtained and processed for in situ hybridization and double-staining techniques. There was a signif icant 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 asthma tics. The expression of alpha IL-5Rm and alpha IL-5Rs was also nonsign ificantly different between the atopic and nonatopic control subjects. However, in the asthmatic subjects, the number of positive cells expr essing mRNA for alpha IL-5Rm inversely correlated with FEV(1) (r(2) = 0.89, p < 0.001), whereas the expression of alpha IL-5Rs mRNA directly correlated with FEV(1) (r(2) = 0.52, p < 0.001). There were no signif icant correlations between alpha IL-5R isoforms and the methacholine P C20. These results suggest that alpha IL-5R upregulation and different ial regulation of alternatively spliced alpha IL-5R mRNA transcripts m ay influence the eosinophil response and the accompanying changes in a irflow limitation in both atopic and nonatopic variants of chronic ast hma.