Characterization of pulmonary immune responses to hyperoxia by high-dimensional mass cytometry analyses.
D HanidziarY NakahoriL A CahillD GalloJ W KeeganJ P NguyenLeo Edmond OtterbeinJ A LedererSimon C RobsonPublished in: Scientific reports (2020)
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.
Keyphrases
- induced apoptosis
- immune response
- dendritic cells
- cell cycle arrest
- oxidative stress
- bone marrow
- transcription factor
- pulmonary hypertension
- adipose tissue
- type diabetes
- metabolic syndrome
- cancer therapy
- lipopolysaccharide induced
- cell proliferation
- peripheral blood
- inflammatory response
- insulin resistance
- long non coding rna
- high fat diet induced