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.

Evidence for Local Eosinophil Differentiation Within Allergic Nasal Mucosa: Inhibition with Soluble IL-5 Receptor

“…ϩ cord blood cells have been shown to produce mainly IL-5R mRNA coding for the soluble isoform of the ␣-chain (18) and Yasruel et al (52) have shown that the expression of sIL-5R␣ mRNA in bronchial biopsies of atopic and nonatopic asthmatics directly correlated with the patients' FEV 1 . As such, factors that induce production of the soluble isoform of the IL-5R may prove highly useful for abrogating eosinophil development as well as other IL-5-mediated events.…”

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

“…The high expression of IL-5R ␣-chain in the bone marrow supports the concept that IL-5 is intricately involved in eosinophilopoiesis, and also one important effect of this cytokine is localized to immature eosinophils bearing IL-5Rs. In humans, it has been shown that mRNA specific for the ␣-chain of IL-5R can be found also in airway tissue (40,51), and it is possible that this mRNA expression leads to IL-5R expression on the cell surface. Certainly, it is likely that airway eosinophils do express small numbers of functionally active IL-5Rs, which, however, are impossible to stain by immunocytochemical techniques.…”

Soluble receptors in human disease

“…In a human clinical correlate, an important component of the allergic response is mediated by eosinophils whose production and activity are significantly stimulated by IL-5. In patients with allergic asthma, the level of mRNA encoding the membranebound IL-5 receptor in endobronchial biopsy samples increases with the severity of bronchial constriction [124]. As treated patients recover from an acute asthmatic episode, expression of soluble IL-5 receptor mRNA increases, suggesting that the soluble IL-5 receptor may counteract the effects of IL-5 in the lung and its increased expression may effect recovery from asthma.…”