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

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; ΔN23-KGF) for the prevention of oedema in lung transplants. Intratracheal instillation of 5 mg·kg-1 ΔN23-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 ΔN23-KGF reduced oedema to a fraction of 1.6±0.8%. In the lavage fluid of pulmonary grafts from ΔN23-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 ΔN23-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. Copyright©ERS Journals Ltd 2008.