Keratinocyte growth factor prevents intraalveolar oedema in experimental lung isografts

¹ Laboratory of Experimental Surgery, Dept of General and Thoracic Surgery, University of Giessen Lung Center, Justus-Liebig-University Giessen, Rudolf-Buchheim-Str. 7, D-35385 Giessen, Germany
² Dept of Internal Medicine, Justus-Liebig-University Giessen, University of Giessen Lung Center, Klinikstr. 36, D-35392 Giessen, Germany
³ Clinical Research Group "Chronic Airway Diseases", Clinic of Internal Medicine (Respiratory Medicine), Philipps University of Marburg, Baldinger-Straße, D-35043 Marburg, Germany
⁴ Fraunhofer Institute of Toxicology and Experimental Medicine, Nicolai-Fuchs-Strasse 1, D-30625 Hannover, Germany

^* To whom correspondence should be addressed. E-mail: Veronika.Grau{at}chiru.med.uni-giessen.de.

	Abstract

Primary graft dysfunction, characterized by intraalveolar oedema, is a major obstacle in pulmonary transplantation. We evaluate the potential of keratinocyte growth factor (palmiferin, N23-KGF) to prevent oedema in lung transplants.

Intratracheal instillation of 5 mg·kg^-1 N23-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 one day later for stereological analysis of intraalveolar oedema and bronchoalveolar lavage. The total protein and phospholipid content as well as surfactant proteins were measured. Surfactant activity was analyzed with a pulsating bubble surfactometer.

In grafts from control treated donors, the fraction of intraalveolar oedema amounted to 3.4±1.1% of the total parenchymal volume. Treatment of donor lungs with N23-KGF reduced oedema to a fraction of 1.6±0.8%. In the lavage fluid of pulmonary grafts from N23-KGF-treated donors, the total protein content was decreased compared to vehicle-treated lung transplants, whereas phospholipids did not differ. The protein fraction contained increased amounts of surfactant protein-C after N23-KGF-treatment and surfactant function was improved.

Treatment of donor lungs with palifermin protects against intraalveolar oedema formation upon transplantation. This effect appears to be mediated by an improved surfactant homeostasis.

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