Characterization of pulmonary immune responses to hyperoxia by high-dimensional mass cytometry analyses
Autor: | Joshua Keegan, D. Gallo, Jennifer P Nguyen, Dusan Hanidziar, Leo E. Otterbein, James A. Lederer, Yasutaka Nakahori, Laura A Cahill, Simon C. Robson |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Myeloid Respiratory distress syndrome lcsh:Medicine Inflammation Hyperoxia Lung injury Biology Article Immunophenotyping Mice 03 medical and health sciences 0302 clinical medicine Immune system Parenchyma medicine Animals Myeloid Cells Lymphocytes lcsh:Science Acute inflammation Diffuse alveolar damage Multidisciplinary Lung lcsh:R Immunity Lung Injury respiratory system Flow Cytometry respiratory tract diseases 3. Good health Disease Models Animal 030104 developmental biology medicine.anatomical_structure Immunology lcsh:Q Disease Susceptibility medicine.symptom Biomarkers 030215 immunology |
Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) |
ISSN: | 2045-2322 |
Popis: | Prolonged exposure to hyperoxia has deleterious effects on the lung, provoking both inflammation and alveolar injury. The elements of hyperoxic injury, which result in high rates of lethality in experimental models, are thought to include multicellular immune responses. To characterize these alterations in immune cell populations, we performed time-of-flight mass cytometry (CyTOF) analysis of CD45-expressing immune cells in whole lung parenchyma and the bronchoalveolar space of mice, exposed to 48 hours of hyperoxia together with normoxic controls. At the tested time point, hyperoxia exposure resulted in decreased abundance of immunoregulatory populations (regulatory B cells, myeloid regulatory cells) in lung parenchyma and markedly decreased proliferation rates of myeloid regulatory cells, monocytes and alveolar macrophages. Additionally, hyperoxia caused a shift in the phenotype of alveolar macrophages, increasing proportion of cells with elevated CD68, CD44, CD11c, PD-L1, and CD205 expression levels. These changes occurred in the absence of histologically evident alveolar damage and abundance of neutrophils in the parenchyma or alveolar space did not change at these time points. Collectively, these findings demonstrate that pulmonary response to hyperoxia involves marked changes in specific subsets of myeloid and lymphoid populations. These findings have important implications for therapeutic targeting in acute lung injury. |
Databáze: | OpenAIRE |
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