MALDI-MSI spatially maps N-glycan alterations to histologically distinct pulmonary pathologies following irradiation
AuthorCarter, Claire L.
Parker, George A.
Hankey, Kim G.
Farese, Ann M.
MacVittie, Thomas J.
Kane, Maureen A.
PublisherSpringer Science and Business Media LLC
MetadataShow full item record
AbstractRadiation-induced lung injury is a highly complex combination of pathological alterations that develop over time and severity of disease development is dose-dependent. Following exposures to lethal doses of irradiation, morbidity and mortality can occur due to a combination of edema, pneumonitis and fibrosis. Protein glycosylation has essential roles in a plethora of biological and immunological processes. Alterations in glycosylation profiles have been detected in diseases ranging from infection, inflammation and cancer. We utilized mass spectrometry imaging to spatially map N-glycans to distinct pathological alterations during the clinically latent period and at 180 days post-exposure to irradiation. Results identified alterations in a number of high mannose, hybrid and complex N-glycans that were localized to regions of mucus and alveolar-bronchiolar hyperplasia, proliferations of type 2 epithelial cells, accumulations of macrophages, edema and fibrosis. The glycosylation profiles indicate most alterations occur prior to the onset of clinical symptoms as a result of pathological manifestations. Alterations in five N-glycans were identified as a function of time post-exposure. Understanding the functional roles N-glycans play in the development of these pathologies, particularly in the accumulation of macrophages and their phenotype, may lead to new therapeutic avenues for the treatment of radiation-induced lung injury. © 2020, The Author(s).
SponsorsU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/13398
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0