School of Paediatrics and Child Health

Luke Garratt

Luke Garratt


Luke Garratt

School of Paediatrics & Child Health
The University of Western Australia
Princess Margaret Hospital for Children
PO Box D 184, Subiaco
WA 6840

Phone (+61) 9340 8625
Fax (+61) 9388 2097


Start Date

February 2011

Submission Date

January 2014

Luke Garratt


Neutrophil elastase mediated disruption of airway epithelial repair in cystic fibrosis Summary


Cystic fibrosis (CF) is an inherited disease where a cell malfunction leads to abnormal amounts of mucous in the lungs, sweat glands and pancreas. This begins from birth and despite best practice care and antibiotic therapy, respiratory disease of infection and inflammation remains common.

The majority of children experience at least one respiratory-related hospitalisation, presenting structural lung changes such as dilated airways and poor ventilation. Changes initially occur without symptoms but these worsen with time, eventually result in lung failure. Data from early life suggests CF airway tissues are not sufficiently repairing damage to the airway epithelium and have linked detection of an enzyme, neutrophil elastase (NE), with this development.

Recent data suggests NE can activate members of the matrix metalloproteinase (MMP) family, powerful modifiers of tissue repair, as well as degrade their inhibitors (TIMPs), leading to a loss of MMP regulation. However, the effect of NE and MMPs on airway repair in CF and their relationship to infection and structural disease remains poorly understood.

The aim of this study is to assess whether chronic NE exposure has a detrimental effect on function and repair of CF airway epithelial cells, as well as investigate the relationship between NE and activation of MMPs in the early CF lung. Subsequent to this, the ability of the NE inhibitor alpha-1 antitrypsin (A1AT) to reverse these effects will be investigated, offering a potential therapy for preventing structural lung disease in early life CF.


  • The University of Western Australia
  • Cystic Fibrosis Western Australia & The McCusker Charitable Foundation
  • Australian Respiratory Early Surveillance Team for CF (AREST CF)

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Last updated:
Monday, 25 August, 2014 5:01 PM