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Asbestos and silica-induced changes in human alveolar macrophage phenotype
A Holian1, M O Uthman, T Goltsova
1Department of Internal Medicine, University of Texas Houston Health Science Center, Houston 77030, USA. aholian@heart.med.uth.tmc.edu
Abstract:
The mechanism by which fibrogenic particulates induce inflammation that can progress to lung fibrosis is uncertain. The alveolar macrophage (AM) has been implicated in the inflammatory process because of its function and reported release of inflammatory mediators when isolated from fibrotic patients. It has been recently shown that fibrogenic, but not nonfibrogenic, particulates are highly potent in inducing apoptosis of human AM. In this study, we tested the hypothesis that fibrogenic particulates could shift the phenotypic ratio of human AM to a more inflammatory condition. The macrophage phenotypes were characterized by flow cytometry targeting the RFD1 and RFD7 epitopes. Results demonstrated that chrysotile and crocidolite asbestos, as well as crystalline silica, but not titanium dioxide or wollastonite, increased the RFD1+ phenotype (inducer or immune activator macrophages) and decreased the RFD1+ RFD7+ phenotype (suppressor macrophages). These results provide a mechanistic explanation that may link apoptosis (namely, suppressor macrophages) to a shift in the ratio of macrophage phenotypes that could initiate lung inflammation.
Insights
Fibrogenic particulates, like asbestos and silica, promote lung inflammation by altering alveolar macrophage phenotypes. This shift from suppressor to immune activator macrophages may drive the progression of lung fibrosis.
Area of Science:
- Pulmonary Medicine
- Immunology
- Toxicology
Background:
- The precise mechanism linking fibrogenic particulates to lung inflammation and fibrosis remains unclear.
- Alveolar macrophages (AMs) are key players in lung inflammation, releasing mediators and showing altered function in fibrotic conditions.
- Fibrogenic particulates induce apoptosis in human AMs, suggesting a role in disease pathogenesis.
Purpose of the Study:
- To investigate if fibrogenic particulates alter the phenotypic ratio of human alveolar macrophages towards a more inflammatory state.
- To explore the potential link between particulate-induced AM apoptosis and changes in macrophage phenotypes.
Main Methods:
- Human alveolar macrophages were exposed to various fibrogenic and non-fibrogenic particulates.
- Macrophage phenotypes were analyzed using flow cytometry, specifically targeting RFD1 and RFD7 epitopes.
Main Results:
- Chrysotile and crocidolite asbestos, and crystalline silica increased the RFD1+ (immune activator) macrophage phenotype.
- These fibrogenic particulates decreased the RFD1+ RFD7+ (suppressor) macrophage phenotype.
- Non-fibrogenic particulates like titanium dioxide and wollastonite did not significantly alter these phenotypes.
Conclusions:
- Fibrogenic particulates induce a shift in human AM phenotypes, favoring immune activation over suppression.
- This phenotypic shift, potentially linked to apoptosis of suppressor macrophages, offers a mechanistic explanation for particulate-induced lung inflammation.
- Findings suggest a pathway from particulate exposure to macrophage dysregulation and the initiation of lung fibrotic disease.