Lipid Uptake by Alveolar Macrophages Drives Fibrotic Responses to Silica Dust.

Authors

Xiaomin Hou, North China University of Science and Technology
Ross Summer, Thomas Jefferson UniversityFollow
Ziying Chen, North China University of Science and Technology
Ying Tian, North China University of Science and Technology
Jingjing Ma, North China University of Science and Technology
Jie Cui, North China University of Science and Technology
Xiaohui Hao, North China University of Science and Technology
Lingli Guo, North China University of Science and Technology
Hong Xu, Thomas Jefferson University; North China University of Science and TechnologyFollow
Hongli Wang, North China University of Science and Technology
Heliang Liu, North China University of Science and Technology

Document Type

Article

Publication Date

1-23-2019

Comments

This article has been peer reviewed. It is the author’s final published version in Scientific Reports, Volume 9, Issue 1, January 2019, Article number 399.

The published version is available at https://doi.org/10.1038/s41598-018-36875-2. Copyright © Hou et al.

Abstract

Silicosis is a common occupational disease and represents a significant contributor to respiratory morbidity and mortality worldwide. Lipid-laden macrophages, or foam cells, are observed in the lungs of patients with silicosis but the mechanisms mediating their formation remain poorly understood. In this study, we sought to elucidate the mechanisms by which silica promotes foam cell formation in the lung, and to determine whether uptake of lipids alone is sufficient to drive TGF-β production by alveolar macrophages. Consistent with previous reports, we found that foam cells were markedly increased in the lungs of patients with silicosis and that these findings associated with both higher levels of intracellular lipid levels (oxidized LDL, ox-LDL) and elevated transcript levels for the lipid scavenger receptor CD36 and the nuclear receptor PPARγ. Employing a rat alveolar macrophage cell line, we found that exposure to silica dust or ox-LDL alone had a modest effect on the induction of foam cell formation and only silica was capable of inducing the production of TGF-β. In contrast, foam cell formation and TGF-β production were both dramatically increased when cells were exposed to a combination of silica dust and ox-LDL. Moreover, we found that these endpoints were markedly attenuated by either blocking CD36 or inhibiting the activity of PPARγ. Altogether, our findings suggest that foam cell formation and TGF-β production are driven by the simultaneous uptake of silica and lipids in alveolar macrophages and that strategies aimed at blocking lipid uptake by alveolar macrophages might be effective in ameliorating fibrotic responses to silica in the lung.

Recommended Citation

Hou, Xiaomin; Summer, Ross; Chen, Ziying; Tian, Ying; Ma, Jingjing; Cui, Jie; Hao, Xiaohui; Guo, Lingli; Xu, Hong; Wang, Hongli; and Liu, Heliang, "Lipid Uptake by Alveolar Macrophages Drives Fibrotic Responses to Silica Dust." (2019). Center for Translational Medicine Faculty Papers. Paper 54.
https://jdc.jefferson.edu/transmedfp/54

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

30674959

Language

English