TY - JOUR
T1 - Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics
AU - Ricciardolo, F. L. M.
AU - Di Stefano, A.
AU - van Krieken, J. H. J. M.
AU - Sont, J. K.
AU - van Schadewijk, A.
AU - Rabe, K. F.
AU - Donner, C. F.
AU - Hiemstra, P. S.
AU - Sterk, P. J.
AU - Mauad, T.
PY - 2003
Y1 - 2003
N2 - 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
AB - 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
U2 - https://doi.org/10.1046/j.1365-2222.2003.01686.x
DO - https://doi.org/10.1046/j.1365-2222.2003.01686.x
M3 - Article
C2 - 12859446
SN - 0954-7894
VL - 33
SP - 905
EP - 911
JO - Clinical and experimental allergy
JF - Clinical and experimental allergy
IS - 7
ER -