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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Cadmium-mediated lung injury is exacerbated by the persistence of classically activated macrophages.

Authors: Larson-Casey, Jennifer L; Gu, Linlin; Fiehn, Oliver; Carter, A Brent

Published In J Biol Chem, (2020 11 13)

Abstract: Heavy metals released into the environment have a significant effect on respiratory health. Lung macrophages are important in mounting an inflammatory response to injury, but they are also involved in repair of injury. Macrophages develop mixed phenotypes in complex pathological conditions and polarize to a predominant phenotype depending on the duration and stage of injury and/or repair. Little is known about the reprogramming required for lung macrophages to switch between these divergent functions; therefore, understanding the mechanism(s) by which macrophages promote metabolic reprogramming to regulate lung injury is essential. Here, we show that lung macrophages polarize to a pro-inflammatory, classically activated phenotype after cadmium-mediated lung injury. Because metabolic adaptation provides energy for the diverse macrophage functions, these classically activated macrophages show metabolic reprogramming to glycolysis. RNA-Seq revealed up-regulation of glycolytic enzymes and transcription factors regulating glycolytic flux in lung macrophages from cadmium-exposed mice. Moreover, cadmium exposure promoted increased macrophage glycolytic function with enhanced extracellular acidification rate, glycolytic metabolites, and lactate excretion. These observations suggest that cadmium mediates the persistence of classically activated lung macrophages to exacerbate lung injury.

PubMed ID: 32917723 Exiting the NIEHS site

MeSH Terms: Animals; Bronchoalveolar Lavage Fluid/immunology; Cadmium/metabolism; Cadmium/toxicity*; Glycolysis/drug effects; Humans; Lipopolysaccharides/pharmacology; Lung Injury/etiology*; Lung Injury/metabolism; Macrophage Activation/drug effects; Macrophages/cytology; Macrophages/drug effects; Macrophages/metabolism*; Mice; Mice, Inbred C57BL; Mitochondria/drug effects; Mitochondria/metabolism; Nitric Oxide Synthase Type II/genetics; Nitric Oxide Synthase Type II/metabolism; PPAR gamma/genetics; PPAR gamma/metabolism; Reactive Oxygen Species/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/metabolism; Up-Regulation

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