Z Yasruel, M Humbert, TC Kotsimbos, Y Ploysongsang, E Minshall, SR Durham, R Pfister, G Menz, J Tavernier, AB Kay and Q Hamid
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

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.

This article has been cited by other articles:

				C. Bergeron and L.-P. Boulet Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest, April 1, 2006; 129(4): 1068 - 1087. [Abstract] [Full Text] [PDF]

				P. Jeffery, S. Holgate, and S. Wenzel Methods for the Assessment of Endobronchial Biopsies in Clinical Research: Application to Studies of Pathogenesis and the Effects of Treatment Am. J. Respir. Crit. Care Med., September 15, 2003; 168(6): S1 - 17. [Full Text] [PDF]

				J. C. Kips, B. J. O'Connor, S. J. Langley, A. Woodcock, H. A. M. Kerstjens, D. S. Postma, M. Danzig, F. Cuss, and R. A. Pauwels Effect of SCH55700, a Humanized Anti-Human Interleukin-5 Antibody, in Severe Persistent Asthma: A Pilot Study Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1655 - 1659. [Abstract] [Full Text] [PDF]

				R. Taha, Q. Hamid, L. Cameron, and R. Olivenstein T Helper Type 2 Cytokine Receptors and Associated Transcription Factors GATA-3, c-MAF, and Signal Transducer and Activator of Transcription Factor-6 in Induced Sputum of Atopic Asthmatic Patients Chest, June 1, 2003; 123(6): 2074 - 2082. [Abstract] [Full Text] [PDF]

				L. Y. Liu, J. B. Sedgwick, M. E. Bates, R. F. Vrtis, J. E. Gern, H. Kita, N. N. Jarjour, W. W. Busse, and E. A. B. Kelly Decreased Expression of Membrane IL-5 Receptor {alpha} on Human Eosinophils: I. Loss of Membrane IL-5 Receptor {alpha} on Airway Eosinophils and Increased Soluble IL-5 Receptor {alpha} in the Airway After Allergen Challenge J. Immunol., December 1, 2002; 169(11): 6452 - 6458. [Abstract] [Full Text] [PDF]

				Leader of the Working Group: M.M. Kelly, Members of the Working Group:, V. Keatings, R. Leigh, C. Peterson, J. Shute, P. Venge, and R. Djukanovic Analysis of fluid{-}phase mediators Eur. Respir. J., July 1, 2002; 20(37_suppl): 24S - 39s. [Full Text] [PDF]

				M.M. Kelly, R. Leigh, S. Carruthers, P. Horsewood, G.J. Gleich, F.E. Hargreave, and G. Cox Increased detection of interleukin-;5 in sputum by addition of protease inhibitors Eur. Respir. J., October 1, 2001; 18(4): 685 - 691. [Abstract] [Full Text] [PDF]

				J.C. Kips Cytokines in asthma Eur. Respir. J., July 2, 2001; 18(34_suppl): 24S - 33s. [Abstract] [Full Text] [PDF]

				J.C. Kips, K.G. Tournoy, and R.A. Pauwels New anti-asthma therapies: suppression of the effect of interleukin (IL)-4 and IL-5 Eur. Respir. J., March 1, 2001; 17(3): 499 - 506. [Abstract] [Full Text] [PDF]

				M. Tomaki, L.-L. Zhao, J. Lundahl, M. Sjostrand, M. Jordana, A. Linden, P. O'Byrne, and J. Lotvall Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor {alpha} J. Immunol., October 1, 2000; 165(7): 4040 - 4050. [Abstract] [Full Text] [PDF]

				A. S. Gounni, B. Gregory, E. Nutku, F. Aris, K. Latifa, E. Minshall, J. North, J. Tavernier, R. Levit, N. Nicolaides, et al. Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils Blood, September 15, 2000; 96(6): 2163 - 2171. [Abstract] [Full Text] [PDF]

				J. Tavernier, J. Van der Heyden, A. Verhee, G. Brusselle, X. Van Ostade, J. Vandekerckhove, J. North, S. M. Rankin, A. B. Kay, and D. S. Robinson Interleukin 5 regulates the isoform expression of its own receptor alpha -subunit Blood, March 1, 2000; 95(5): 1600 - 1607. [Abstract] [Full Text] [PDF]

				L. Cameron, P. Christodoulopoulos, F. Lavigne, Y. Nakamura, D. Eidelman, A. McEuen, A. Walls, J. Tavernier, E. Minshall, R. Moqbel, et al. Evidence for Local Eosinophil Differentiation Within Allergic Nasal Mucosa: Inhibition with Soluble IL-5 Receptor J. Immunol., February 1, 2000; 164(3): 1538 - 1545. [Abstract] [Full Text] [PDF]

				S. Esnault and J. S. Malter Primary Peripheral Blood Eosinophils Rapidly Degrade Transfected Granulocyte-Macrophage Colony-Stimulating Factor mRNA J. Immunol., November 15, 1999; 163(10): 5228 - 5234. [Abstract] [Full Text] [PDF]

				K F Chung and P J Barnes Cytokines in asthma Thorax, September 1, 1999; 54(9): 825 - 857. [Full Text]

				M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]