Keratinocyte growth factor prevents intra-alveolar oedema in experimental lung isografts.
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.
Sadovski
J
J
Laboratory of Experimental Surgery, Dept of General and Thoracic Surgery, University of Giessen Lung Center, Justus-Liebig-University Giessen, Giessen, Germany.
Kuchenbuch
T
T
Ruppert
C
C
Fehrenbach
A
A
Hirschburger
M
M
Padberg
W
W
Günther
A
A
Hohlfeld
J M
JM
Fehrenbach
H
H
Grau
V
V
D000818:Animals; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D004487:Edema / Q000473:pathology* / Q000517:prevention & control; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism*; D006706:Homeostasis; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D010455:Peptides; D010743:Phospholipids; D051523:Fibroblast Growth Factor 7; C077063:Sftpc protein, rat