title: Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics.
abstract: Eosinophil-derived TGF-beta 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-beta1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-beta1 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-beta1 and the concentration of TGF-beta1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins.
authors.affiliation: Department of Allergy and Clinical Immunology, Imperial College London, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: Flood-Page
authors.forename: Andrew
authors.initials: A
authors.lastname: Menzies-Gow
authors.forename: Simon
authors.initials: S
authors.lastname: Phipps
authors.forename: Sun
authors.initials: S
authors.lastname: Ying
authors.forename: Arun
authors.initials: A
authors.lastname: Wangoo
authors.forename: Mara S
authors.initials: MS
authors.lastname: Ludwig
authors.forename: Neil
authors.initials: N
authors.lastname: Barnes
authors.forename: Douglas
authors.initials: D
authors.lastname: Robinson
authors.forename: A Barry
authors.initials: AB
authors.lastname: Kay
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000378:metabolism / Q000628:therapy*; D001485:Basement Membrane / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D004311:Double-Blind Method; D004804:Eosinophils / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D007632:Keratan Sulfate / Q000032:analysis; D000071234:Lumican; D012333:RNA, Messenger; D019063:Tenascin / Q000032:analysis; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011508:Chondroitin Sulfate Proteoglycans; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D015848:Interleukin-5; C000604306:LUM protein, human; D000071234:Lumican; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D019063:Tenascin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007632:Keratan Sulfate; C434107:mepolizumab