Ozone-derived oxysterols impair lung macrophage phagocytosis via adduction of some phagocytosis receptors.

Abstract

Inhalation of the ambient air pollutant ozone causes lung inflammation and can suppress host defense mechanisms, including impairing macrophage phagocytosis. Ozone reacts with cholesterol in the lung to form oxysterols, like secosterol A and secosterol B (SecoA and SecoB), which can form covalent adducts on cellular proteins. How oxysterol-protein adduction modifies the function of lung macrophages is unknown. Herein, we used a proteomic screen to identify lung macrophage proteins that form adducts with ozone-derived oxysterols. Functional ontology analysis of the adductome indicated that protein binding was a major function of adducted proteins. Further analysis of specific proteins forming adducts with SecoA identified the phagocytic receptors CD206 and CD64. Adduction of these receptors with ozone-derived oxysterols impaired ligand binding and corresponded with reduced macrophage phagocytosis. This work suggests a novel mechanism for the suppression of macrophage phagocytosis following ozone exposure through the generation of oxysterols and the formation of oxysterol-protein adducts on phagocytic receptors.

• Authors: Parker F Duffney, Hye-Young H Kim, Ned A Porter, Ilona Jaspers
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 295 Issue 36 Pg. 12727-12738 (09 04 2020) ISSN: 1083-351X [Electronic] United States
• PMID: 32690608 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2020 Duffney et al.

Chemical References

• FCGR1A protein, human
• MRC1 protein, human
• Membrane Glycoproteins
• Oxysterols
• Receptors, IgG
• Receptors, Immunologic
• secosterol-B
• Ozone
• Cholesterol

Topics

• Cholesterol (analogs & derivatives, metabolism)
• Humans
• Lung (cytology, metabolism)
• Macrophages (cytology, metabolism)
• Membrane Glycoproteins (metabolism)
• Oxysterols (metabolism)
• Ozone (metabolism)
• Phagocytosis
• Receptors, IgG (metabolism)
• Receptors, Immunologic (metabolism)
• THP-1 Cells