Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics

Flood-Page, P., Menzies-Gow, A., Phipps, S., Ying, S., Wangoo, A., Ludwig, M. S., Barnes, N., Robinson, D. and Kay, A. B. (2003) Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. Journal of Clinical Investigation, 112 7: 1029-1036.


Author Flood-Page, P.
Menzies-Gow, A.
Phipps, S.
Ying, S.
Wangoo, A.
Ludwig, M. S.
Barnes, N.
Robinson, D.
Kay, A. B.
Title Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
1558-8238
Publication date 2003-10
Sub-type Article (original research)
DOI 10.1172/JCI200317974
Volume 112
Issue 7
Start page 1029
End page 1036
Total pages 8
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Formatted abstract Eosinophil-derived TGF-β has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti-IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. The thickness and density of tenascin, lumican, and procollagen III in the reticular basement membrane (RBM) were quantified immunohistochemically by confocal microscopy. Expression of TGF-β1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-β1 protein was measured in bronchoalveolar lavage (BAL) fluid by ELISA. At baseline, airway eosinophil infiltration and ECM protein deposition was increased in the RBM of asthmatics compared with nonasthmatic controls. Treating asthmatics with anti-IL-5 antibody, which specifically decreased airway eosinophil numbers, significantly reduced the expression of tenascin, lumican, and procollagen III in the bronchial mucosal RBM when compared with placebo. In addition, anti-IL-5 treatment was associated with a significant reduction in the numbers and percentage of airway eosinophils expressing mRNA for TGF-β1 and the concentration of TGF-β1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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