Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Alveolar Macrophage ABCG1 Deficiency Promotes Pulmonary Granulomatous Inflammation.

Authors: McPeek, Matthew; Malur, Anagha; Tokarz, Debra A; Lertpiriyapong, Kvin; Gowdy, Kymberly M; Murray, Gina; Wingard, Christopher J; Fessler, Michael B; Barna, Barbara P; Thomassen, Mary Jane

Published In Am J Respir Cell Mol Biol, (2019 09)

Abstract: Pulmonary granuloma formation is a complex and poorly understood response to inhaled pathogens and particulate matter. To explore the mechanisms of pulmonary granuloma formation and maintenance, our laboratory has developed a multiwall carbon nanotube (MWCNT)-induced murine model of chronic granulomatous inflammation. We have demonstrated that the MWCNT model closely mimics pulmonary sarcoidosis pathophysiology, including the deficiency of alveolar macrophage ATP-binding cassette (ABC) lipid transporters ABCA1 and ABCG1. We hypothesized that deficiency of alveolar macrophage ABCA1 and ABCG1 would promote pulmonary granuloma formation and inflammation. To test this hypothesis, the effects of MWCNT instillation were evaluated in ABCA1, ABCG1, and ABCA1/ABCG1 myeloid-specific knockout (KO) mice. Histological examination revealed significantly larger pulmonary granulomas in ABCG1-KO and ABCA1/ABCG1 double-KO animals when compared with wild-type animals. Evaluation of BAL cells indicated increased expression of CCL2 and osteopontin, genes shown to be involved in the formation and maintenance of pulmonary granulomas. Single deficiency of alveolar macrophage ABCA1 did not affect MWCNT-induced granuloma formation or proinflammatory gene expression. These observations indicate that the deficiency of alveolar macrophage ABCG1 promotes pulmonary granulomatous inflammation and that this is augmented by additional deletion of ABCA1.

PubMed ID: 30848658 Exiting the NIEHS site

MeSH Terms: ATP Binding Cassette Transporter 1/genetics*; ATP Binding Cassette Transporter, Subfamily G, Member 1/deficiency*; ATP-Binding Cassette Transporters/genetics; Animals; Granuloma/metabolism; Inflammation/metabolism*; Lung/metabolism; Macrophages, Alveolar/metabolism*; Mice, Knockout; Pneumonia/metabolism; Sarcoidosis, Pulmonary/metabolism*

Back
to Top