D prostanoid receptor 2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells.
Bottom Line: The effects of the selective DP2 agonist 13, 14-dihydro-15-keto prostaglandin D2 on epithelial cell migration and differentiation were determined.Numbers of submucosal DP2(+) cells were increased in asthmatic patients compared with those in healthy control subjects (mean [SEM]: 78  vs 22 /mm(2) submucosa, P < .001).DP2 is expressed by the bronchial epithelium, and its activation drives epithelial differentiation, suggesting that in addition to its well-characterized role in inflammatory cell migration, DP2 might contribute to airway remodeling in asthmatic patients.
Affiliation: Institute of Lung Health, Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, United Kingdom.Show MeSH
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Mentions: To determine whether a change in phenotype had occurred in the DP2− epithelial cells, we costained cells with involucrin, which was previously described as a reliable marker of a squamous metaplastic phenotype by Araya et al23 in the lungs of patients with COPD. We found a lack of DP2 staining on epithelial cells in areas expressing pancytokeratin (used to confirm epithelial origin) and involucrin (Fig 2, A-C). Many of the DP2− epithelial cells had a flattened squamous morphology (Fig 2, C). These findings suggested that the reduction in DP2+ epithelial cell counts was due to a metaplastic change in phenotype of the epithelial cells in the groups with moderate and severe asthma. Epithelial histology for all biopsy specimens were graded according to the criteria shown in Fig 2, D. Grading criteria were assessed on 2 separate occasions, and intraclass correlation for all data was strong (Cronbach α = .992, P < .001). A significant increase in epithelial histology grade was observed for biopsy specimens from patients with moderate and severe asthma compared with that seen in healthy control samples (median [interquartile range]: grade 4 [2-4] vs grade 1.5 [1-2], P < .001; grade 4 [3-4] vs grade 1.5 [1-2], P < .001) and biopsy specimens from patients with moderate and severe asthma compared with those from patients with mild asthma (grade 4 [2-4] vs grade 2 [1-3], P < .001; grade 4 [3-4] vs grade 2 [1-3], P < .001; Fig 2, D). Quantification of a change in phenotype of some epithelial cells was achieved by using involucrin staining graded with the criteria described in Fig 2, E. A significantly higher incidence of involucrin staining was observed for biopsy specimens from patients with moderate and severe asthma compared with healthy control samples (grade 3 [2-3] vs grade 0 [0-1], P < .001; grade 3 [2-3] vs grade 0 [0-1], P < .001; Fig 2, E) and biopsy specimens from patients with severe asthma compared with those from patients with mild asthma (grade 3 [2-3] vs grade 1 [0-2], P = .026). The number of DP2+ epithelial cells was negatively correlated with both the histology grade and involucrin grade (rs = −0.63, rs = −0.69, P < .001; see Figs E4 and E5 in this article's Online Repository at www.jacionline.org).
Affiliation: Institute of Lung Health, Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, United Kingdom.