Lee, Do Hyang;
(2023)
The response of ciliated cells to particulates and the immune response of the nasal airway epithelium.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Mucociliary clearance (MCC) is a major host defence against millions of particles inhaled into the human lung. Inhaling particles contains air pollutants and pathogens, and especially pollutant particle exposure is strongly linked to lung diseases. Ciliated epithelium plays a critical role in MCC, although the immediate interaction of particles with the ciliated epithelium remains unclear. This study aimed to investigate the effect of immediate interaction, focusing on particle binding to motile airway cilia. To mimic the human airway environment in vitro, ciliated epithelial cell cultures and aerosol particle delivery models are essential. Hence, a robust ciliated culture method was determined by using a combination of mouse embryonic fibroblast (3T3-J2) feeder cells and Rho-associated protein kinase (ROCK) inhibitor to grow a large number of basal cells from nasal biopsies obtained from healthy individuals and patients with primary ciliary dyskinesia (PCD). It was shown that large numbers of basal cells can be generated by using this method. Furthermore, differentiated basal cells at the air-liquid interface (ALI) were shown the ultrastructural defect on cilia from PCD, which confirmed the disease phenotypes of PCD were maintained. Following further study investigated how the inhaled particulates interact with the nasal epithelial cells by developing two systems (nebulisation and pMDI/spacer) to deliver aerosolised fluticasone propionate (FP) particles. Aerosol-delivered FP particles bound to the tips of motile airway cilia, with many remaining bound for at least 24 hours. The FP binding reduced ciliary beat amplitude while maintaining ciliary beat frequency. Following the findings to explore further the effect of particle binding and its impact on the cellular response, the interaction of amorphous silica particles and motile airway cilia was studied. The binding was affected by charge with greater binding using positive particles. The binding again reduced ciliary beat amplitude and activated NF-κB. The immune response, assessed by cytokine and chemokine release, suggested a differential response to particle delivery to asthma and healthy cultures with, unexpectedly, a greater inflammatory response in healthy cultures.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The response of ciliated cells to particulates and the immune response of the nasal airway epithelium |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10175785 |
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