- Title
- The role of Fc gamma receptor and Fc gamma receptor-mediated phagocytosis in asthma
- Creator
- Gupta, Sachin
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2022
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Fc gamma receptors (FcγRs) are expressed on the surface of phagocytic cells such as monocytes, macrophages, and neutrophils. FcγRs play an essential role in identifying and attaching the phagocytes to opsonised pathogens, facilitating opsonic phagocytosis. Alteration in expression of FcγRs is seen in several diseases, such as upregulation of activator FcγRs as observed in rheumatoid arthritis and systemic lupus erythematosus, resulting in inflammation. However, FcγR expression is not known in asthma. Phagocytosis by alveolar macrophages is impaired in asthma, resulting in persistent and recurrent airway bacterial infection in some people with asthma. In laboratory experiments, it was demonstrated that infection of alveolar macrophages and monocyte-derived macrophages with rhinovirus impairs the phagocytosis of bacteria. However, the mechanism by which rhinovirus impairs bacterial phagocytosis is not known. In Chapter 3 of this thesis, we characterised the FcγR expression (FcγRI, FcγRIIA, FcγRIIB and FcγRIII) on blood monocytes and monocyte subsets in people with asthma having different asthma severity and healthy controls. We show that FcγRIII expression on non-classical monocytes is upregulated in asthma, particularly in non-severe and non-eosinophilic asthma. In Chapter 4 of this thesis, we evaluated the effect of asthma-associated stimuli – Rhinovirus 16 (RV16) and interleukin-33 (IL-33) – on the FcγR expression (FcγRI, FcγRIIA, FcγRIIB and FcγRIII) on monocytes in people with asthma and healthy controls. We show that the presence of asthma did not have any role in the FcγR expression (FcγRI, FcγRIIA, FcγRIIB and FcγRIII) in response to RV16 and IL-33. However, RV16 and IL-33 modulate the FcγR expression on monocytes independent of disease status both in people with asthma and healthy controls. In Chapter 5 of this thesis, we characterised the FcγR expression (FcγRI, FcγRIIA, FcγRIIB and FcγRIII) on monocyte-derived macrophages and FcγR-mediated phagocytosis in people with asthma and healthy controls and showed that there is no difference in the FcγR expression and opsonic phagocytosis. This study also examined the effect of RV16 infection on bacterial phagocytosis by monocyte-derived macrophages. The study demonstrated that RV16 exposure to monocyte-derived macrophages does not impair bacterial phagocytosis.
- Subject
- Fc gamma receptors; asthma; phagocytosis; severe asthma; monocytes and macrophages
- Identifier
- http://hdl.handle.net/1959.13/1513424
- Identifier
- uon:56718
- Rights
- Copyright 2022 Sachin Gupta
- 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 | 292 KB | Adobe Acrobat PDF | View Details Download |