Abstract

Background: Nasal polyp (NP) is a chronic upper airway inflammatory disease that is frequently triggered by defective host-defense. However, the mechanisms underlying the impaired barrier function such as cilia-mediated mucociliary clearance remain poorly understood. Objective: To assess ciliary ultrastructural and ciliogenesis marker expression and the phenotypes of ciliated cells in NP. Methods: NP biopsy samples were obtained from 97 NP patients and inferior turbinate from 32 healthy controls. Immunofluorescence staining, quantitative polymerase chain reaction, and single-cell cytospin staining were performed. We classified the patterns of radial spoke head protein (RSPH) 1, 4A (RSPH4A), 9 (RSPH9), and dynein axonemal heavy chain 5 (DNAH5) localization. A semi-quantitative scoring system was developed to assess their expression patterns and associations with ciliogenesis markers [centrosomal protein 110 (CP110) and forkhead box j1 (FOXJ1)]. Results: Median scores of RSPH1, RSPH4A, RSPH9, and DNAH5 were significantly higher in NP than in healthy controls, particularly in eosinophilic NPs. Expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5 correlated positively with each other in both groups. In primary-cell specimens, abnormal expression patterns were significantly more common in NP. The total fluorescence intensity of CP110 and FOXJ1 was significantly higher in NPs and correlated positively with expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5. A trend towards lengthened cilia was observed in NP. Conclusion: In the chronic airway inflammatory milieu, the up-regulated ciliogenesis correlates with the abnormal expression of ciliary ultrastructural markers (i.e., DNAH5) in NP (particularly eosinophilic NP).

Highlights

  • Nasal polyp (NP) is a common chronic upper airway inflammatory disorder that frequently co-exists with lower airway inflammatory diseases such as asthma (Fokkens et al, 2012)

  • Median scores of RSPH1, RSPH4A, RSPH9, and dynein axonemal heavy chain 5 (DNAH5) were significantly higher in NP than in healthy controls, in eosinophilic NPs

  • The total fluorescence intensity of centrosomal protein 110 (CP110) and fork-head box J1 (FOXJ1) was significantly higher in NPs and correlated positively with expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5

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Summary

Introduction

Nasal polyp (NP) is a common chronic upper airway inflammatory disorder that frequently co-exists with lower airway inflammatory diseases such as asthma (Fokkens et al, 2012). We have previously demonstrated the poorly proliferated basal cells and up-regulation of ciliogenesis markers [centrosomal protein 110 (CP110), and fork-head box J1 (FOXJ1)] in the aberrantly remodeled epithelium of NP (Li et al, 2014; Zhao et al, 2017). Abnormal ciliogenesis and/or ultrastructure might be critical drivers of impaired mucociliary clearance (MCC), contributing to the chronic inflammation in NPs. Nasal polyp (NP) is a chronic upper airway inflammatory disease that is frequently triggered by defective host-defense. The mechanisms underlying the impaired barrier function such as cilia-mediated mucociliary clearance remain poorly understood

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