Lipidomic dysregulation within the lung parenchyma following whole-thorax lung irradiation: Markers of injury, inflammation and fibrosis detected by MALDI-MSI
PublisherNature Publishing Group
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AbstractRadiation-induced lung injury (RILI) is a delayed effect of acute radiation exposure that can limit curative cancer treatment therapies and cause lethality following high-dose whole-thorax lung irradiation (WTLI). To date, the exact mechanisms of injury development following insult remain ill-defined and there are no FDA approved pharmaceutical agents or medical countermeasures. Traditionally, RILI development is considered as three phases, the clinically latent period, the intermediate acute pneumonitis phase and the later fibrotic stage. Utilizing matrix-assisted laser desorption ionization mass spectrometry imaging, we identified a number of lipids that were reflective of disease state or injury. Lipids play central roles in metabolism and cell signaling, and thus reflect the phenotype of the tissue environment, making these molecules pivotal biomarkers in many disease processes. We detected decreases in specific surfactant lipids irrespective of the different pathologies that presented within each sample at 180 days post whole-thorax lung irradiation. We also detected regional increases in ether-linked phospholipids that are the precursors of PAF, and global decreases in lipids that were reflective of severe fibrosis. Taken together our results provide panels of lipids that can differentiate between naïve and irradiated samples, as well as providing potential markers of inflammation and fibrosis. Copyright 2017 The Author(s).
SponsorsThis project has been funded with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201000046C, and from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under subcontract to Contract No: HHSO100201100007C, Aeolus Pharmaceuticals, Inc. (Mission Viejo, CA).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85028881317&doi=10.1038%2fs41598-017-10396-w&partnerID=40&md5=2406313618bb361ef7eafb82e41be2d3; http://hdl.handle.net/10713/11268