Neutrophil phenotype and function in ocular inflammatory disorders

Murad, Mariam ORCID: 0000-0002-2343-4800 (2021). Neutrophil phenotype and function in ocular inflammatory disorders. University of Birmingham. Ph.D.

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Ocular inflammatory diseases are the result of the breakdown of protective ocular barriers. Behçet's disease (BD) and Ocular mucous membrane pemphigoid (OcMMP) are chronic inflammatory eye disorders, in which neutrophils have been implicated in their pathogenesis. In this thesis the phenotype and function of neutrophils from patients with these diseases was assessed.
Peripheral blood neutrophils were obtained from patients with BD, OcMMP and healthy controls. Percoll isolation was used to isolate all neutrophils, while Ficoll-Hypaque was used to obtain subpopulations. Phagocytic capacity and production of reactive oxygen species (ROS), neutrophil extracellular traps (NETs) and heterogeneity were assessed in all populations.
Neutrophils from both patient cohorts showed a reduced phagocytic capacity and ROS production, but greater NET production by total neutrophils compared to cells from healthy controls. Also, patients had elevated numbers of low density and lower number of normal density neutrophils, but showed a similar phenotype as total neutrophils. Granulocytic myeloid-suppressor cells were evident within the Low density neutrophil (LDN) and Normal density neutrophil (NDN) population of both patient cohorts when compared healthy controls.
The results suggest that a chronic inflammatory state reduces phagocytosis and ROS production but increases NET production in circulatory neutrophils. Therefore, Further analysis of neutrophil heterogeneity may explain these phenotypic and functional differences.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Wallace, Graham
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Inflammation and Ageing
Funders: Other
Other Funders: Hale-Rudd
Subjects: R Medicine > RE Ophthalmology


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