Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury in a large animal model

Item originally deposited in University of Edinburgh, Edinburgh Research Explorer Repository at: https://www.research.ed.ac.uk/portal/en/publications/nebulisation-of-synthetic-lamellar-lipids-mitigates-radiationinduced-lung-injury-in-a-large-animal-model(ab917c99-7e7f-4fa1-8d1e-40511ca9abd3).htmlMethods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3–4 days intervals) to a defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation. Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep. Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.This work was supported by Grant MRC/CIC3/025 awarded to D.C., J.L., J.M., G.M. & J.P. The authors wish to acknowledge the assistance of Dryden Animal Services in the conduct of this work, and the assistance of Dr Helen Brown in relation to experimental design and statistical analysis. The authors are grateful to Lamellar Biomedical Ltd., Strathclyde Business Park, Bellshill, Scotland, United Kingdom, for the supply of LAMELLASOME™ used in this research.8pubpubArticle no: 1331