E-Thesis 106 views 112 downloads
Disentangling the Effects of Nitrogen Dioxide and Particulates in Air Pollution on Human Health: A Mechanistic Toxicological Approach / Josh Bateman
Swansea University Author: Josh Bateman
DOI (Published version): 10.23889/SUthesis.68916
Abstract
The ambient levels of particulate matter (PM) and nitrogen dioxide (NO2), two major pollutants within both outdoor and indoor air, are typically proportional given that they are often emitted from the same sources, such as motor vehicles and industry. Epidemiological studies have linked inhalation e...
| Published: |
Swansea, Wales, UK
2025
|
|---|---|
| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Clift, Martin J. D. |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa68916 |
| Abstract: |
The ambient levels of particulate matter (PM) and nitrogen dioxide (NO2), two major pollutants within both outdoor and indoor air, are typically proportional given that they are often emitted from the same sources, such as motor vehicles and industry. Epidemiological studies have linked inhalation exposure of each pollutant to adverse pulmonary health effects, although difficulty lies in distinguishing the pollutant-specific effects due to their co-emission. These health effects could be determined by assessing either pollutant type within the same experimental system. To address this research gap, an in vitro co-culture model of the alveolar barrier comprising alveolar type 1 cells (hAELVi), alveolar type 2 cells (NCI-H441) and alveolar macrophages (differentiated THP-1) was characterised. Through culturing at the air-liquid interface, the co-culture was examined after pollutant co-exposures to PM (aerosol exposure) and NO2 (using a novel NO2 exposure unit). Standardised PM samples of carbon black, urban dust, indoor dust, as well as freshly captured diesel emission particles were chosen based on their relevance to human exposure. The ability of each pollutant to affect cytotoxicity, barrier function, pro-inflammatory responses, oxidative stress, and the transcriptome (via RNA sequencing) was evaluated. The results showed that both PM and NO2 can act in a pro-inflammatory manner, shown through IL6 and IL8 release (via ELISA). In contrast, confocal microscopy revealed that NO2 induced morphological changes, which could be indicative of phenotypic alterations, especially in NCI-H441 cells. Co-exposure of PM samples with NO2 was shown to amplify PM-induced cytotoxicity and the pro-inflammatory response. RNA-sequencing uncovered a potential synergistic mechanism behind this effect, where NO2 inhibits anti-inflammatory mechanisms, allowing PM to induce an augmented pro-inflammatory response. In conclusion, this work suggests that differing constituents of air pollution may be able to act synergistically to amplify airway inflammation. However, this was shown to be dependent upon the source of the PM. These results highlight the importance of considering the toxicological effects of air pollution both independently and in relation to each other, an important factor when considering the reduction of air pollution exposure to improve the burden upon public health. |
|---|---|
| Keywords: |
Air Pollution, Toxicology, In Vitro, Nitrogen Dioxide, Particulate Matter |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
UK Health Security Agency (previously Public Health England) |