Palmer, Lisa Joanne (2010)
Ph.D. thesis, University of Birmingham.
This thesis has investigated the role of neutrophil extracellular traps (NETs) in the pathogenesis of periodontitis. A fluorometric assay was developed for the in vitro quantification of NET release and used to assess relative levels in chronic periodontitis patients, indicating elevated release under several stimulatory conditions compared with controls. Studies also demonstrated that challenge with periodontitis-associated bacteria evoked differential NET release. In addition, an extensive panel of periodontal pathogens was screened for two potential virulence traits that may confer a survival advantage when challenged with NETs. Deoxyribonuclease (DNase) secretion, capable of degrading NETs, and resistance to killing by histone, a core structural and antimicrobial protein within NETs, were both shown to be relatively common characteristics possessed by pathogens associated with severe disease. Additionally, an in vivo study demonstrated DNase activity in plaque and GCF during the development of experimental gingivitis. Further studies examined the association between neutrophil reactive oxygen species production and NET release implicating a regulatory role for myeloperoxidase generated hypochlorous acid in NET production. In conclusion, the results contained within this thesis indicate a putative role for NETs in the pathogenesis of periodontitis and highlight a high prevalence of potential counter-NET mechanisms in certain periodontal organisms.
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