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 journalArticle


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
Issue number7
Publication statusPublished - Jul 1 2003



  • Asthma
  • Epithelium
  • Proliferation and inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Ricciardolo, F. L. M., Di Stefano, A., Van Krieken, J. H. J. M., Sont, J. K., Van Schadewijk, A., Rabe, K. F., Donner, C. F., Hiemstra, P. S., Sterk, P. J., & Mauad, T. (2003). Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics. Clinical and Experimental Allergy, 33(7), 905-911.