Abstract
The nasal epithelium represents the first line of defense against inhaled pathogens, allergens, and irritants and plays a key role in the pathogenesis of a spectrum of acute and chronic airways diseases. Despite age-dependent clinical phenotypes triggered by these noxious stimuli, little is known about how aging affects the structure and function of the airway epithelium that is crucial for lung homeostasis and host defense. The aim of this study was therefore to determine age-related differences in structural and functional properties of primary nasal epithelial cultures from healthy children and non-smoking elderly people. To achieve this goal, highly differentiated nasal epithelial cultures were established from nasal brushes at air–liquid interface and used to study epithelial cell type composition, mucin (MUC5AC and MUC5B) expression, and ion transport properties. Furthermore, we determined age-dependent molecular signatures using global proteomic analysis. We found lower numeric densities of ciliated cells and higher levels of MUC5AC expression in cultures from children vs. elderly people. Bioelectric studies showed no differences in basal ion transport properties, ENaC-mediated sodium absorption, or CFTR-mediated chloride transport, but detected decreased calcium-activated TMEM16A-mediated chloride secretory responses in cultures from children vs. elderly people. Proteome analysis identified distinct age-dependent molecular signatures associated with ciliation and mucin biosynthesis, as well as other pathways implicated in aging. Our data identified intrinsic, age-related differences in structure and function of the nasal epithelium and provide a basis for further studies on the role of these findings in age-dependent airways disease phenotypes observed with a spectrum of respiratory infections and other noxious stimuli.
Highlights
The airway mucosa represents the first line of defense of the respiratory system against pathogens, pollutants, and irritants that are constantly inhaled during tidal breathing
We found a lower number of ciliated cells in cultures from children compared to elderly people and higher number of MUC5AC+ cells, while the number of basal cells did not differ between age groups (Figures 1C–E)
This study provides an integrated comparison of age-related differences in the cell-type composition, mucin expression, ion transport properties, and the proteome of highly differentiated primary nasal epithelial cultures from children and elderly people
Summary
The airway mucosa represents the first line of defense of the respiratory system against pathogens, pollutants, and irritants that are constantly inhaled during tidal breathing. At the interface with the environment, airway epithelial cells have developed specialized functions to provide host protection, such as barrier function, secretion of anti-microbial mediators, interaction with cells of the immune system, as well as elimination of potentially harmful stimuli by mucociliary clearance (MCC) [1, 2]. MCC operates through the coordinated function of (i) the motile cilia, (ii) the airway surface liquid layer, and (iii) the mucus layer [3–6]. Proper MCC is crucial for airway homeostasis, and mucociliary dysfunction has been implicated in the pathogenesis of acute and chronic airways diseases caused by a spectrum of pathogens, allergens, and other environmental pollutants [4, 12]. The clinical airways disease phenotypes triggered by some of these noxious stimuli are strikingly age-dependent, suggesting a potential role of agerelated differences in airway epithelial defense properties [13– 20]. The relationship between age and airway epithelial structure and function has not been studied
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