Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics

Fabio L M Ricciardolo, A. Di Stefano, J. H J M Van Krieken, J. K. Sont, A. Van Schadewijk, K. F. Rabe, C. F. Donner, P. S. Hiemstra, P. J. Sterk, T. Mauad

Research output: Contribution to journalArticlepeer-review

Abstract

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 crossover 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.

Original languageEnglish
Pages (from-to)905-911
Number of pages7
JournalClinical and Experimental Allergy
Volume33
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

Keywords

  • Asthma
  • Epithelium
  • Proliferation and inflammation

ASJC Scopus subject areas

  • Immunology

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