- Title
- Characterization of neutrophil subsets in obstructive airway disease
- Creator
- Lokwani, Ravi
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2020
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Obstructive airway diseases (OADs) such as asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis are common respiratory diseases, and their prevalence is expected to increase further. The presence of airway inflammation is a common feature of OADs that contributes to its exacerbation and airway remodelling. Neutrophils are important innate immune cells of our immune system and, as a phagocyte, play a vital role in the defence against microorganisms. Neutrophils possess granules that contain cytotoxic proteins required for killing of pathogens such as bacteria and fungi. The spillage of these cytotoxic contents in inflamed tissues can also damage host tissue and further aggravate the host’s clinical condition. The recruitment of these cells in airways against immune insult and injury is a standard procedure of our innate immune system and required for the resolution of infection or inflammation. However, the dysregulated and continuous influx of these cells in airways can cause mucous hypersecretion, airway obstruction and airway remodelling, which can further contribute to pathogenesis of OADs such as asthma, COPD and bronchiectasis. While significant developments have taken place in the treatment of eosinophil-dominated inflammation in OADs, neutrophil-dominated inflammation still lacks specific therapeutic options. The developments in targeted therapies against neutrophil recruitment in airways have been met with safety challenges and have failed to deliver promising treatment outcomes. Neutrophils were considered a homogeneous population of phagocytes until a recent study by Pillay et al. showed the presence of more than one type of neutrophil in systemic circulation after inducing an acute systemic inflammation. The study showed the presence of three different subsets of neutrophil consisting of banded neutrophils with a single banded nucleus, normal neutrophils with segmented nucleus (two to four lobes) and hypersegmented neutrophils with a further segmented nucleus (more than four lobes). These neutrophils also featured different expressions of CD16 and CD62L surface molecules. In Chapter 3 of this thesis, we characterise neutrophils on the basis of their nucleus morphology following the definitions from Pillay et al. in bronchial lavage (BL) samples and validate the presence of these neutrophil subsets in the airways of participants with OAD and in healthy controls. We also show the increased presence of hypersegmented neutrophils and their association with reduced lung function and airway obstruction in participants with OAD. In Chapter 4, we characterise the OAD participants of Chapter 3, on the basis of the proportion and number of hypersegmented neutrophils and measure the inflammatory mediators (interleukins 8, 6 and 1β) in the BL supernatants of these participants. We also show the association of hypersegmented neutrophils with levels of inflammatory mediators. In Chapter 5, we measure the surface adhesion molecule, oxidative burst and CD62L shedding of blood neutrophils of OAD (asthma and COPD) and healthy controls, and show the presence of a primed phenotype of neutrophil in COPD participants. Moreover, we also characterise and show the neutrophil subsets based on their surface expression by using the definitions of Pillay et al. in the systemic circulation of all three cohorts (asthma, COPD and healthy).
- Subject
- neutrophils; neutrophils subsets; obstructive airway disease; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1412158
- Identifier
- uon:36436
- Rights
- Copyright 2020 Ravi Lokwani
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 424 KB | Adobe Acrobat PDF | View Details Download |