Keratinocyte growth factor prevents intra-alveolar oedema in experimental lung isografts

Eur Respir J. 2008 Jan;31(1):21-8. doi: 10.1183/09031936.00011707. Epub 2007 Oct 10.

Abstract

Primary graft dysfunction, characterised by intra-alveolar oedema, is a major obstacle in pulmonary transplantation. The present study evaluates the potential of keratinocyte growth factor (palmiferin; DeltaN23-KGF) for the prevention of oedema in lung transplants. Intratracheal instillation of 5 mg x kg(-1) DeltaN23-KGF was performed in Lewis rats on days 3 and 2 before explantation. Control animals obtained an equivalent volume of vehicle. Left lungs were isogeneically transplanted and the graft recipients were sacrificed 1 day later for stereological analysis of intra-alveolar oedema and bronchoalveolar lavage. The total protein and phospholipid content, as well as surfactant proteins, were measured. Surfactant activity was analysed with a pulsating bubble surfactometer. In grafts from control treated donors, the fraction of intra-alveolar oedema amounted to 3.4+/-1.1% of the total parenchymal volume. Treatment of donor lungs with DeltaN23-KGF reduced oedema to a fraction of 1.6+/-0.8%. In the lavage fluid of pulmonary grafts from DeltaN23-KGF-treated donors, the total protein content was decreased compared with vehicle-treated lung transplants, whereas phospholipids did not differ. The protein fraction contained increased amounts of surfactant protein-C after DeltaN23-KGF treatment and surfactant function was improved. Treatment of donor lungs with palifermin protects against intra-alveolar oedema formation upon transplantation. This effect appears to be mediated by an improved surfactant homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid
  • Edema / pathology*
  • Edema / prevention & control
  • Fibroblast Growth Factor 7 / metabolism*
  • Homeostasis
  • Lung / metabolism
  • Lung / pathology*
  • Lung Transplantation / methods*
  • Male
  • Models, Biological
  • Peptides / chemistry
  • Phospholipids / chemistry
  • Pulmonary Alveoli / metabolism
  • Rats
  • Rats, Inbred Lew

Substances

  • Peptides
  • Phospholipids
  • Fibroblast Growth Factor 7
  • Sftpc protein, rat