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Thorax 2009;64:156-161 doi:10.1136/thx.2008.102814
  • Interstitial lung disease

Soluble endostatin is a novel inhibitor of epithelial repair in idiopathic pulmonary fibrosis

  1. A G Richter1,
  2. S McKeown3,
  3. S Rathinam5,
  4. L Harper2,
  5. P Rajesh5,
  6. D F McAuley3,
  7. R Heljasvaara4,
  8. D R Thickett1
  1. 1
    Lung Injury and Fibrosis Treatment Programme, Department of Medical Sciences, Medical School, University of Birmingham, Birmingham, UK
  2. 2
    Department of Renal Immunobiology, Division of Infection and Immunity, Medical School, University of Birmingham, Birmingham, UK
  3. 3
    Respiratory Medicine Research Group, The Queen’s University of Belfast, Belfast, UK
  4. 4
    Collagen Research Unit, Biocentre Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland
  5. 5
    Department of Thoracic Surgery, Heart of England NHS trust, Birmingham, UK
  1. Dr D Thickett, c/o Lung Investigation Unit, 1st floor Nuffield House, Birmingham B15 2TH, UK; d.thickett{at}bham.ac.uk
  • Received 6 June 2008
  • Accepted 3 September 2008
  • Published Online First 13 October 2008

Abstract

Background and aim: Aberrant angiogenesis and defective epithelial repair are key features of idiopathic pulmonary fibrosis (IPF). Endostatin is an antiangiogenic peptide with known effects on endothelial cells. This study aimed to establish the levels of endostatin in the bronchoalveolar lavage fluid (BALF) in IPF and to investigate its actions on distal lung epithelial cells (DLEC) and primary type II cells.

Methods: 20 patients with IPF and 10 controls underwent BAL. Endostatin was measured by ELISA. BALF cytokines and matrix metalloproteinase (MMP)-3 were measured by Luminex array. Primary DLEC monolayers were wounded and treated with endostatin. Apoptosis and cell viability were assessed.

Results: Endostatin was elevated in the BALF and plasma of patients with IPF compared with normal controls. There was a negative correlation between endostatin, forced vital capacity and gas transfer. Endostatin correlated with a number of proinflammatory cytokines and MMP3. Physiological endostatin doses inhibited DLEC wound repair by 44% in an effect that was partially FasL and caspase dependent. Endostatin increased apoptosis rates by 8% and reduced their viability by 34%. Similar effects of endostatin were seen in primary type II cells in terms of inhibition of wound repair and proliferation.

Conclusions: Elevated BALF endostatin levels correlated with a number of elevated cytokines, MMP3 and lung function in IPF. Endostatin is a novel inhibitor of DLEC wound repair, inducing apoptosis and reducing cell viability in a FasL and caspase dependent manner. Endostatin may play a role in aberrant epithelial repair in IPF.

Footnotes

  • Funding: AR was funded by a Wellcome CRF Entry Level Fellowship. DRT is funded by a Wellcome Intermediate Fellowship.

  • Competing interests: None.

  • Ethics approval: This study was approved by the local ethics committee.

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  4. All Versions of this Article:
    1. thx.2008.102814v1
    2. 64/2/156 most recent

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