Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics

Ricciardolo, Fabio Luigi Massimo; Stefano, Antonino Di; Krieken, J. Han J.M. van; Sont, Jacob K.; Schadewijk, Annemarie van; Rabe, Klaus F.; Cf, Donner; Hiemstra, Pieter S.; Sterk, Peter J.; Mauad, Thaís

doi:10.1046/j.1365-2222.2003.01686.x

Cited by 34 publications

(24 citation statements)

References 50 publications

(61 reference statements)

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“…This proliferative response may be triggered by persistent airway inflammation, viral infection, or injury in the genetically susceptible individual. Some researchers have demonstrated an increase in epithelial proliferation in conjunction with eosinophilic inflammation after allergen challenge (37). We have previously demonstrated a prominent proliferative response associated with persistent airway hyperreactivity that developed in the setting of paramyxoviral infection (44).…”

Section: Discussionmentioning

confidence: 93%

“…This difference in the epithelium does not appear to be due to the presence or lack of epithelial desquamation (Figure 1 and Reference 36). Ricciardolo and colleagues demonstrated that allergen challenge appears to increase epithelial proliferation in subjects with mild asthma (37). Few studies have examined differences in airway remodeling in subjects with severe asthma.…”

Section: Discussionmentioning

confidence: 99%

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Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma

Cohen

Xueping

Tarsi

et al. 2007

Am J Respir Crit Care Med

215

161

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Rationale: Despite long-term therapy with corticosteroids, patients with severe asthma develop irreversible airway obstruction. Objectives: To evaluate if there are structural and functional differences in the airway epithelium in severe asthma associated with airway remodeling. Methods: In bronchial biopsies from 21 normal subjects, 11 subjects with chronic bronchitis, 9 subjects with mild asthma, and 31 subjects with severe asthma, we evaluated epithelial cell morphology: epithelial thickness, lamina reticularis (LR) thickness, and epithelial desquamation. Levels of retinoblastoma protein (Rb), Ki67, and Bcl-2 were measured, reflecting cellular proliferation and death. Terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) was used to study cellular apoptosis. Measurements and Main Results: Airway epithelial and LR thickness was greater in subjects with severe asthma compared with those with mild asthma, normal subjects, and diseased control subjects (p ϭ 0.009 and 0.033, respectively). There was no significant difference in epithelial desquamation between groups. Active, hypophosphorylated Rb expression was decreased (p ϭ 0.002) and Ki67 was increased (p Ͻ 0.01) in the epithelium of subjects with severe asthma as compared with normal subjects, indicating increased cellular proliferation. Bcl-2 expression was decreased (p Ͻ 0.001), indicating decreased cell death suppression. There was a greater level of apoptotic activity in the airway biopsy in subjects with severe asthma as compared with the normal subjects using the TUNEL assay (p ϭ 0.002), suggesting increased cell death. Conclusions: In subjects with severe asthma, as compared with subjects with mild asthma, normal subjects, and diseased control subjects, we found novel evidence of increased cellular proliferation in the airway contributing to a thickened epithelium and LR. These changes may contribute to the progressive decline in lung function and airway remodeling in patients with severe asthma.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma

Cohen

Xueping

Tarsi

et al. 2007

Am J Respir Crit Care Med

215

161

View full text Add to dashboard Cite

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“…Interestingly, in the present study Ki-67+ epithelial cell numbers in small airways correlated with neutrophils, suggesting a link between inflammation and tissue remodelling. Accordingly, increased Ki-67+ epithelial cells following allergen challenge were related in asthma to airway eosinophilia [39]. Alternatively, these correlations could be due to the presence of intra-epithelial inflammatory cells expressing Ki-67 antigen.…”

Section: Discussionmentioning

confidence: 96%

Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD

Pilette¹,

Colinet²,

Kiss³

et al. 2007

European Respiratory Journal

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Galectins-1 and -3 regulate epithelial proliferation/apoptosis and neutrophil activation, and are implicated in lung cancer and asthma. The role of galectins in chronic obstructive pulmonary disease (COPD), characterised by epithelial changes and neutrophil infiltration, remains unknown.In the present study, galectin-1 and -3 expression was assessed by immunohistology in the bronchial epithelium of lung specimens from eight severe COPD patients and compared with nine nonsmokers and six smokers without COPD. Findings were related to epithelial proliferation (Ki-67), tissue inflammation and lung function.Epithelial galectin-3 immunostaining was increased only in the small airways of COPD patients when compared with nonsmokers and smokers. In contrast, galectin-1 was only significantly increased in the small airways of the group of smokers. Ki-67+ epithelial cells and neutrophils were increased in the small airways of COPD patients when compared with smokers. Furthermore, intra-epithelial neutrophils correlated in the small airways with Ki-67+ epithelial cells and with the forced expiratory volume in one second/forced vital capacity ratio. However, no correlation was observed with galectin expression.The present study supports the hypothesis that distal airways represent an important site for detecting changes in chronic obstructive pulmonary disease. In patients with severe disease, an increased galectin-3 expression and neutrophil accumulation in the small airway epithelium was demonstrated, correlating with epithelial proliferation and airway obstruction.

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“…Both genetic and environmental factors as well as their interactions are involved in asthma development and its course during lifetime. Recent advances in the understanding of the pathophysiology of asthma have pointed towards a prominent role of the airway epithelium in asthma development and severity [3,4].…”

mentioning

confidence: 99%

E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids

Ierodiakonou

Postma

Koppelman

et al. 2011

European Respiratory Journal

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E-cadherins form intercellular junctions that maintain epithelial integrity. Epithelial integrity is impaired in asthma and can be restored by inhaled corticosteroids (ICSs). Our aim was to investigate the association of CDH1 gene polymorphisms (single-nucleotide polymorphisms (SNPs)) with airway remodelling, inflammation and forced expiratory volume in 1 s (FEV1) decline in asthma patients and assess whether ICSs modulate these effects.Bronchial biopsies of 138 asthmatics were available (population 1). Associations of 17 haplotype-tagging SNPs with epithelial E-cadherin expression, biopsy parameters and FEV1/vital capacity (VC) ratio were tested. FEV1 and VC data were collected in 281 asthmatics with 30-yr follow-up (population 2). Linear mixed-effect models were used to assess associations of SNPs with FEV1 decline.Seven out of the 17 SNPs were associated with airway remodelling, three with CD8+ T-cell counts, two with eosinophil counts and seven with FEV1 decline. All associations occurred only in patients using ICS. In general, alleles associated with less remodelling correlated with less FEV1 decline and higher FEV1/VC. Decreased epithelial E-cadherin expression was associated with five SNPs in non-ICS users.In conclusion, our data show that CDH1 polymorphisms are associated with epithelial Ecadherin expression and suggest that epithelial adhesion is an important contributor to airway remodelling and lung function in asthma. These effects are modified by the use of inhaled corticosteroids.

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Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics

Abstract: 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.

Cited by 34 publications

References 50 publications

Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma

Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma

Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD

E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids

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