Exploring the aberrant phenotype of neutrophils in periodontitis

Badlishah Sham, Nurul Iman (2020). Exploring the aberrant phenotype of neutrophils in periodontitis. University of Birmingham. Ph.D.

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Abstract

Neutrophils, the most abundant leukocyte arrive at the site of infections to eliminate pathogens, particularly by using reactive oxygen species (ROS). They contain the antioxidant glutathione (GSH) to maintain homeostasis and combat ROS induced intracellular damage. Intracellular GSH is essential for a number of homeostatic and cellular processes, including chemotaxis and is the main intracellular redox buffer. During oxidative stress, protein modification by glutathionylation helps defend against oxidative damage.

The aim of this work was to investigate the role of redox balance in the aberrant chemotactic phenotype observed in neutrophils, particularly from periodontitis patients.

In healthy neutrophils, GSH modulating compounds (buthionine sulfoximine, N-acetylcysteine, carmustine and 1-chloro, 2-4 dinitrobenzene) were used to change GSH levels: showing that decreased GSH was associated with a decreased chemotactic ability. In periodontitis patients there was less GSH in neutrophils in comparison to healthy donors but it increased after successful non-surgical treatment. A similar pattern was observed for neutrophil chemotaxis. This demonstrated a link between these two factors in the same cells for the first time. Proteomic analysis of extracts from patient and control neutrophils demonstrated modulation of glutathione regulation in periodontitis patients.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):