title: Membrane-bound and soluble alpha IL-5 receptor mRNA in the bronchial mucosa of atopic and nonatopic asthmatics.
abstract: 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.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Yasruel
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: T C
authors.initials: TC
authors.lastname: Kotsimbos
authors.forename: Y
authors.initials: Y
authors.lastname: Ploysongsang
authors.forename: E
authors.initials: E
authors.lastname: Minshall
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: R
authors.initials: R
authors.lastname: Pfister
authors.forename: G
authors.initials: G
authors.lastname: Menz
authors.forename: J
authors.initials: J
authors.lastname: Tavernier
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D015848:Interleukin-5 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D053649:Receptors, Interleukin-5
chemical_list: D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5