Nasal Epithelial Cells as Surrogates for Bronchial Epithelial Cells in Airway Inflammation Studies

Abstract

The nose is an attractive source of airway epithelial cells, particularly in populations in which bronchoscopy may not be possible. However, substituting nasal cells for bronchial epithelial cells in the study of airway inflammation depends upon comparability of responses, and evidence for this is lacking. Our objective was to determine whether nasal epithelial cell inflammatory mediator release and receptor expression reflect those of bronchial epithelial cells. Paired cultures of undifferentiated nasal and bronchial epithelial cells were obtained from brushings from 35 subjects, including 5 children. Cells were subject to morphologic and immunocytochemical assessment. Mediator release from resting and cytokine-stimulated cell monolayers was determined, as was cell surface receptor expression. Nasal and bronchial cells had identical epithelial morphology and uniform expression of cytokeratin 19. There were no differences in constitutive expression of CD44, intercellular adhesion molecule-1, alphavbeta3, and alphavbeta5. Despite significantly higher constitutive release of IL-8, IL-6, RANTES (regulated on activation, normal T cell expressed and secreted), and matrix metalloproteinase (MMP)-9 from nasal compared with bronchial cells, the increments in release of all studied mediators in response to stimulation with IL-1beta and TNF-alpha were similar, and there were significant positive correlations between nasal and bronchial cell secretion of IL-6, RANTES, vascular endothelial growth factor, monocyte chemoattractant protein-1, MMP-9, and tissue inhibitor of metalloproteinase-1. Despite differences in absolute mediator levels, the responses of nasal and bronchial epithelial cells to cytokine stimulation were similar, expression of relevant surface receptors was comparable, and there were significant correlations between nasal and bronchial cell mediator release. Therefore, nasal epithelial cultures constitute an accessible surrogate for studying lower airway inflammation.

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

“…Stimulation with TNF-α resulted in a greater increase in the IL-6 level in bronchial cells. Our results differ from those of other researchers [25]. McDougall et al showed comparable levels of IL-6 in cultures of bronchial and nasal epithelial cells after TNF-α and IL-1β stimulation (median 163 vs. 179 pg/ml, respectively).…”

“…Only a few studies have compared the pro-inflammatory abilities of the nasal and bronchial epithelial cells. Experiments with cultures of paired undifferentiated nasal and bronchial epithelial cells obtained from patients suffering from various respiratory disorders showed differences in the production of IL-6, CXCL8 and numerous mediators of inflammation in response to TNF-α and IL-1β [25]. Comer et al showed that nasal epithelial cells obtained from COPD subjects could not be used as a substitute for bronchial epithelial cells for in vitro studies due to the substantially different IL-6 release [26].…”

Upper airway. 3: Sinonasal involvement in chronic obstructive pulmonary disease

“…Obtaining nasal biopsies is much less invasive, can be repeated more readily, and similarities between the pathological findings in COPD nasal and bronchial biopsies have been described above. 19 A recent study has also demonstrated that cell surface marker expression and functional responses of matched, cultured nasal and bronchial cells are similar, 32 and some of the subjects recruited to this study had COPD. This builds on earlier work demonstrating that nasal and bronchial epithelial cell cultures are of similar size and shape, and have similar growth rates and ciliary beat frequency.…”

Analysis of Short and Long Term Variability of Nasal Mucus versus Breath Condensate Inflammation Markers in Healthy Individuals

“…The concentrations of the nasal inflammation markers were approximately 1000 times higher than the concentrations in EBC. McDougall et al [24] and Pringle et al [25] reported that some nasal epithelial cells' mediators such as IL-8 and IL-6 had an increased constitutive expression compared to bronchial epithelial cells [24,25].…”