Article Text

PDF

Mechanisms of chronic lung disease
P113 Secreted Lysyl Oxidase is Elevated in the Bronchoalveolar Lavage Fluid of Patients with Idiopathic Pulmonary Fibrosis
  1. CJ Calderwood1,
  2. MG Jones1,
  3. L Hoile2,
  4. T Havelock2,
  5. TM Maher3,
  6. KMA O’Reilly2,
  7. DE Davies1
  1. 1University of Southampton, Southampton, United Kingdom
  2. 2Southampton University Hospitals NHS Trust, Southampton, United Kingdom
  3. 3Royal Brompton Hospital, London, United Kingdom

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease for which there are no effective treatments. As a result the prognosis is poor, with a median survival of 3 years from the onset of symptoms. The key feature of IPF is formation of ‘fibroblastic foci’, accumulations of highly active, proliferative fibroblasts and myofibroblasts that lay down vast quantities of collagen and other extracellular matrix proteins. Lysyl oxidase (LOX) is a secreted enzyme involved in cross-linking of collagen and implicated in several fibrotic conditions. Increased cross-linking due to LOX upregulation in IPF may contribute to decreased lung compliance. Further, LOX may represent a biomarker that can be used to detect early responses or ‘proof-of-mechanism’ in clinical trials for new IPF drugs. We hypothesized that levels of LOX protein were higher in bronchoalveolar lavage (BAL) fluid from IPF patients compared to healthy controls.

Methods BAL fluid was collected from patients with IPF or volunteers following ethical approval and informed consent. A quantity of BAL fluid determined to contain 20μg protein was concentrated with Strataclean resin and resuspended in 2x sample buffer. LOX protein content was determined by SDS-PAGE and western blotting followed by densitometry.

Results LOX can be detected in BAL fluid from patients with IPF. Both pro and active forms of the LOX enzyme are significantly elevated in IPF compared to healthy controls, with active LOX detected in 12/25 IPF patients compared to 1/9 healthy controls.

Conclusions There is increasing evidence for a role of LOX in fibrosis. Here we suggest LOX may be involved in IPF pathogenesis, and demonstrate that it is possible to detect secreted LOX in BAL fluid from patients with this condition. LOX may therefore represent a biomarker that could be used in clinical trials for IPF . Further work would be required to validate and optimise assays for clinical use.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.