Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics

• Published in: Clinical and experimental allergy 2003-07, Vol.33 (7), p.905-911
• Main Authors: Ricciardolo, F. L. M., Stefano, A. Di, Krieken, J. H. J. M. van, Sont, J. K., Schadewijk, A. van, Rabe, K. F., Donner, C. F., Hiemstra, P. S., Sterk, P. J., Mauad, T.
• Format: Article
• Language: English
• Subjects: Adult; Allergens; Allergic diseases; Antigens, Neoplasm - metabolism; asthma; Asthma - pathology; Asthma - physiopathology; Biological and medical sciences; Bronchi; Bronchitis - pathology; Cadherins; Cell Adhesion Molecules - metabolism; Cell Division; Cross-Over Studies; Dust; Epithelial Cell Adhesion Molecule; epithelium; Female; Forced Expiratory Volume - physiology; Humans; Immunohistochemistry; Immunopathology; Ki-67 Antigen - metabolism; Male; Medical sciences; proliferation and inflammation; Respiratory and ent allergic diseases; Respiratory Mucosa - pathology
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2003.01686.x

Summary Background The mechanisms that regulate epithelial integrity and repair in asthma are poorly understood. We hypothesized that allergen exposure could alter epithelial inflammation, damage and proliferation in atopic asthma. Objective We studied epithelial cell infiltration, shedding, expression of the proliferation marker Ki‐67 and the epithelial cell–cell adhesion molecules Ep‐CAM and E‐cadherin in bronchial biopsies of 10 atopic mild asthmatics 48 h after experimental diluent (D) and allergen (A) challenge in a cross‐over design. Methods Epithelial shedding, expressed as percentage of not intact epithelium, Ki‐67+, eosinophil/EG‐2+, CD4+ and CD8+ cells were quantified by image analysis in bronchial epithelium, and adhesion molecules were analysed semi‐quantitatively. Results Epithelial shedding was not altered by A (D: 88.1±3.1% vs. A: 89.2±3.7%; P=0.63). The numbers of Ki‐67+ epithelial (D: 10.2±0.2 vs. A: 19.9±0.3 cells/mm; P=0.03), EG‐2+ (D: 4.3±0.5 vs. A: 27±0.3 cells/mm; P=0.04) and CD4+ cells (D: 1.7±1.2 vs. A: 12.3±0.6 cells/mm; P=0.04) were significantly increased after A, whilst CD8+ numbers were not significantly changed (P>0.05). E‐cadherin and Ep‐CAM epithelial staining showed a similar intensity after D and A (P>0.05). We found a positive correlation between EG‐2+ and Ki‐67+ cells in the epithelium (Rs: 0.63; P=0.02). Conclusion Our study indicates that allergen challenge increases epithelial proliferation in conjunction with inflammation at 2 days after exposure. This favours the hypothesis that long‐lasting epithelial restitution is involved in the pathogenesis of asthma.