Ling, Martin Robert
(2015).
Neutrophil function in chronic periodontitis.
University of Birmingham.
Ph.D.
Abstract
Neutrophil function in the pathogenesis of chronic periodontitis was investigated. A case-controlled longitudinal intervention study of patients with chronic periodontitis and matched healthy controls was performed. Peripheral blood neutrophils from patients released more IL-8, IL-6, IL-1β and TNF-α in response to periodontally-relevant bacteria than controls. Hyper-reactive \(Fusobacterium\) \(nucleatum\)-stimulated neutrophil IL-8, IL-6 and TNF-α release from patient cells normalised to control levels following successful therapy. Hyper-reactive FcγR-stimulated IL-8, IL-6, IL-1β and TNF-α and \(Porphyromonas\) \(gingivalis\)-stimulated IL-1β release by patient cells persisted after therapy. Patient neutrophils displayed hyper-active and hyper-reactive superoxide release that normalised to healthy control levels post-therapy. Although neutrophil extracellular trap release was unchanged in periodontitis, patient neutrophils demonstrated impaired directional chemotactic accuracy, speed and velocity. Studies on control neutrophils demonstrated that physiologically-relevant concentrations of C-reactive protein (CRP) inhibited baseline reactive oxygen species (ROS) generation, and reduced FcγR–stimulated superoxide and \(F.\) \(nucleatum\)-stimulated luminol/isoluminol detectable ROS. However, CRP enhanced \(F.\) \(nucleatum\)-stimulated neutrophil superoxide release. The data demonstrate that chronic periodontitis is characterised by dysregulated neutrophil function, notably heightened cytokine and superoxide production and impaired chemotaxis. Furthermore, mildly elevated CRP levels in periodontitis could play a role in modifying the neutrophil respiratory burst and provide a link with periodontitis-associated systemic disease.
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