Neutrophil elastase mediated disruption of airway epithelial repair

    Research output: ThesisDoctoral Thesis

    572 Downloads (Pure)

    Abstract

    [Truncated] Cystic fibrosis (CF) is a life-threatening genetic disease, caused by autosomal recessive mutations in the CF transmembrane conductance regulator (CFTR) gene. Incidence varies globally but CF is a rare disease that predominantly affects Caucasian populations. An ion channel expressed on apical surfaces of many epithelial tissues, the mutation phenotype of defective electrolyte transport and mucosal function begins very early in life and predominates in the lungs, sweat glands and pancreas. Respiratory disease is common and by school age, the majority of children experience at least one respiratory-related hospitalisation and often exhibit structural lung disease, particularly bronchiectasis and air trapping. These changes are typically independent of clinical symptoms and worsen with time.

    Progressive lung disease in CF indicates that the airway tissues are not sufficiently repairing chronic damage. Therefore, identifying and treating the mechanisms of poor airway repair in CF could delay disease progression. To date, proteases including the immune cell protease neutrophil elastase (NE) and members of matrix metalloproteinase (MMP) family, which are powerful modifiers of tissues and extracellular matrix, have been implicated in contributing to structural CF airway disease. The paediatric Australian Respiratory Early Surveillance Team for CF (AREST CF) program recently identified that uninhibited NE activity in bronchoalveolar lavage fluid (BALf), was the best predictor in infants for later development of bronchiectasis.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Supervisors/Advisors
    • Kicic, Anthony, Supervisor
    • Stick, Stephen, Supervisor
    • Sutanto, Erika, Supervisor
    • Devadason, Sunalene, Supervisor
    Publication statusUnpublished - 2015

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