Continuous mucociliary transport by primary human airway epithelial cells in vitro

Sears, Patrick R.; Yin, Weining; Ostrowski, Lawrence E.

doi:10.1152/ajplung.00024.2015

Cited by 65 publications

(81 citation statements)

References 48 publications

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“…These histological findings can be of important in understanding the pathogenesis causing acute and chronic airway infection and inflammation, clinical symptoms of coughing and expectoration, and give more evidences to the current "vicious cycle hypothesis". MCC is characterized by the upward movement of mucus by ciliary motion that requires a balance between the volume and composition of the mucus, and normal ciliary beat frequency (17,18). In our study, we showed hyperplasia and/or hypertrophy of the goblet cells in both the large and small airways epithelium, which contributed directly to the over-secretion of the mucus and impairment of MCC in the patients.…”

Section: Discussionsupporting

confidence: 49%

“…In our study, we showed hyperplasia and/or hypertrophy of the goblet cells in both the large and small airways epithelium, which contributed directly to the over-secretion of the mucus and impairment of MCC in the patients. Mucus production, secretion and clearance play a critical role in maintenance of airway health because it maintains hydration in the airway and traps particulates, bacteria, and viruses (18,19). Furthermore, airway goblet cells are proinflammatory effector cells which are able to secrete pro-inflammatory cytokines, chemokines, and growth factors.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings therefore present pathological evidences to the current "vicious cycle hypothesis" in the development of bronchiectasis. Although different types of epithelial cells contribute to the MCC function, ciliated cells play a central role in maintaining MCC function and preventing chronic airway diseases (18,22). Among the tissue specimens, significantly lengthened cilia are present on the hyperplasic epithelium both in bronchi and bronchioles.…”

Section: Discussionmentioning

confidence: 99%

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Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Chen

Wang

et al. 2018

J. Thorac. Dis.

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Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis.Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed.Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) μm, P<0.0001; bronchioles: 7.46 (6.41-8.48) μm, P<0.0001] as compared to nonhyperplastic epithelium (bronchi: 5.60 μm; bronchioles: 4.89 μm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%).Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Chen

Wang

et al. 2018

J. Thorac. Dis.

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“…Fully differentiated human bronchial epithelial (hBE) cells were cultured on an air-liquid interface (ALI) track model with established mucus production, mucus secretion, and muco-ciliary transport in order to more closely model in vivo airway physiology [15]. Endogenous mucus flow was verified using light microscopy prior to imaging.…”

Section: Methodsmentioning

confidence: 99%

Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments

et al. 2016

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Mucus hydration (wt%) has become an increasingly useful metric in real-time assessment of respiratory health in diseases like cystic fibrosis and COPD, with higher wt% indicative of diseased states. However, available in vivo rheological techniques are lacking. Gold nanorods (GNRs) are attractive biological probes whose diffusion through tissue is sensitive to the correlation length of comprising biopolymers. Through employment of dynamic light scattering theory on OCT signals from GNRs, we find that weakly-constrained GNR diffusion predictably decreases with increasing wt% (more disease-like) mucus. Previously, we determined this method is robust against mucus transport on human bronchial epithelial (hBE) air-liquid interface cultures (R2=0.976). Here we introduce diffusion-sensitive OCT (DS-OCT), where we collect M-mode image ensembles, from which we derive depth- and temporally-resolved GNR diffusion rates. DS-OCT allows for real-time monitoring of changing GNR diffusion as a result of topically applied mucus-thinning agents, enabling monitoring of the dynamics of mucus hydration never before seen. Cultured human airway epithelial cells (Calu-3) with a layer of endogenous mucus were doped with topically deposited GNRs (80×22nm), and subsequently treated with hypertonic saline (HS) or isotonic saline (IS). DS-OCT provided imaging of the mucus thinning response up to a depth of 600μm with 4.65μm resolution, over a total of 8 minutes in increments of ≥3 seconds. For both IS and HS conditions, DS-OCT captured changes in the pattern of mucus hydration over time. DS-OCT opens a new window into understanding mechanisms of mucus thinning during treatment, enabling real-time efficacy feedback needed to optimize and tailor treatments for individual patients.

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“…Although, the changes in CBF observed after increasing the viscosity in the presence of TNF α represent a decay of up to 30% of the CBF with respect to basal CBF, it is well established that MCC velocity is directly dependent on CBF and that small changes in CBF have a substantial effects on MCC effectiveness [34]. …”

Section: Discussionmentioning

confidence: 99%

TNFαAffects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium

González

Droguett

Ríos

et al. 2016

BioMed Research International

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In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca+2 level ([Ca2+]i). We studied the effect of TNFα on the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue. Cultures were treated with TNFα, before and after the viscous load was changed. TNFα treatment produced a significantly larger decrease in CBF in cultures exposed to dextran. Furthermore, an increment in [Ca2+]i was observed, which was significantly larger after TNFα treatment. In conclusion, although TNFα has deleterious effects on ciliated cells in response to maintaining CBF after increasing viscous loading, it has a positive effect, since increasing [Ca2+]i may prevent the MCC collapse. These findings suggest that augmented levels of TNFα associated with an inflammatory response of the nasopharyngeal epithelium may have dual effects that contribute to maintaining the effectiveness of MCC in the upper airways.

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Continuous mucociliary transport by primary human airway epithelial cells in vitro

Abstract: Sears PR, Yin W, Ostrowski LE. Continuous mucociliary transport by primary human airway epithelial cells in vitro.

Cited by 65 publications

References 48 publications

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments

TNFαAffects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium

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