Membrane-bound and soluble alpha IL-5 receptor mRNA in the bronchial mucosa of atopic and nonatopic asthmatics.
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.
Yasruel
Z
Z
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Humbert
M
M
Kotsimbos
T C
TC
Ploysongsang
Y
Y
Minshall
E
E
Durham
S R
SR
Pfister
R
R
Menz
G
G
Tavernier
J
J
Kay
A B
AB
Hamid
Q
Q
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
D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5