Background: Aberrant airway epithelial remodeling is one of the cardinal histopathologic features of inflammatory airway diseases, but whether it alters the mucociliary apparatus remains unknown.
Objective: We sought to investigate the morphologic pattern of motile cilia and ciliogenesis-associated makers in hyperplastic nasal epithelium from nasal polyps (NPs) both in vivo and in vitro.
Methods: Biopsy specimens obtained from patients with NPs (n = 44) and inferior turbinate from healthy control subjects (n = 38) were analyzed by using scanning electron microscopy, immunofluorescence staining, single-cell (cytospin) staining, quantitative real-time PCR, and human nasal epithelial stem/progenitor cell culture and differentiation.
Results: Abnormal cilia architecture (untidy, overly dense, and lengthened) was more commonly observed in patients with NPs by using scanning electron microscopy. Ectopic lengthened cilia were visualized by means of immunofluorescence (patients with NPs: 6.33 μm [5.51-7.43 μm] vs control subjects: 3.73 μm [3.50-4.27 μm], P < .0001), at the site of epithelial hyperplasia in isolated single cells (patients with NPs: 6.55 ± 0.23 μm vs control subjects 4.89 ± 0.24 μm, P < .0001), and in differentiated ciliated cells derived from human nasal epithelial stem/progenitor cells (patients with NPs: 9.20 ± 0.56 μm vs control subjects: 5.21 ± 0.37 μm, P < .0001). Ciliary beat frequency was found to be significantly slower in patients with NPs than control subjects in vitro. Both protein and mRNA levels of ciliogenesis-associated markers (centrosomal protein 110 [CP110], forkhead box J1 [Foxj1], and P73 isoform with an N-terminal transactivation domain [TAp73]) were significantly increased in patients with NPs versus those seen in control subjects and were positively correlated with cilia length.
Conclusion: For the first time, this study demonstrates for that motile cilia impairment is a co-condition of epithelial hyperplasia in patients with NPs, and this impairment of function is a likely cause of chronic mucosal inflammation or infection (eg, biofilm) observed in patients with chronic rhinosinusitis.
Keywords: Impairments of cilia architecture; hyperplasia; nasal polyps.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.