1. ABCG1 and ABCG4 as key transporters in the development of pulmonary alveolar proteinosis by nanoparticles.
- Author
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Jeon S, Kim SH, Jeong J, Lee DK, Lee S, Kim S, Kim G, Maruthupandy M, and Cho WS
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 1, ATP-Binding Cassette Transporters genetics, Animals, Macrophages, Alveolar, Rats, ATP Binding Cassette Transporter, Subfamily G genetics, Nanoparticles toxicity, Pneumonia, Pulmonary Alveolar Proteinosis genetics
- Abstract
Pulmonary alveolar proteinosis (PAP) has been reported in rodents treated with nanoparticles (NPs). However, little is known about the type of NPs producing PAP and their toxicity mechanisms. Here, we assembled seven PAP-inducing NPs and TiO
2 NPs as a negative control. At 1 and 6 months after a single intratracheal instillation in rats, pulmonary inflammation and the gene expression of ATP-binding cassette (ABC) transporters and related genes were evaluated in separated alveolar macrophages (AMs). One month after intratracheal instillation, seven NPs (Eu2 O3 , In2 O3 , Pr6 O11 , Sm2 O3 , Tb4 O7 , and NiO) caused PAP, but only In2 O3 NPs caused persistent PAP at 6 months after treatment. The levels of phospholipids, indicators of PAP, showed good correlations with the gene expression profile of five transporters (ABCA1, ABCB4, ABCB8, ABCG1, and ABCG4), which effluxing phospholipids in AMs. Among them, ABCG1 and ABCG4 might be key transporters involved in PAP development because both showed a negative correlation with the magnitude of PAP, while others might be compensatory transporters for PAP recovery, as they showed a positive correlation. In conclusion, the identification of seven PAP-producing NPs implies that PAP may be an emerging occupational disease and that ABCG1 and ABCG4 may be therapeutic targets for PAP., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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