Biomaterial Database

Ozone-derived oxysterols impair lung macrophage phagocytosis via adduction of some phagocytosis receptors. 2020

Parker F Duffney, and Hye-Young H Kim, and Ned A Porter, and Ilona Jaspers

Curriculum in Toxicology, Departments of Pediatrics and Microbiology and Immunology, Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina, USA.

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.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D010126	Ozone	The unstable triatomic form of oxygen, O3. It is a powerful oxidant that is produced for various chemical and industrial uses. Its production is also catalyzed in the ATMOSPHERE by ULTRAVIOLET RAY irradiation of oxygen or other ozone precursors such as VOLATILE ORGANIC COMPOUNDS and NITROGEN OXIDES. About 90% of the ozone in the atmosphere exists in the stratosphere (STRATOSPHERIC OZONE).	Ground Level Ozone,Low Level Ozone,Tropospheric Ozone,Level Ozone, Ground,Level Ozone, Low,Ozone, Ground Level,Ozone, Low Level,Ozone, Tropospheric
D010587	Phagocytosis	The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).	Phagocytoses
D011971	Receptors, Immunologic	Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.	Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072376	Oxysterols	Oxygenated derivatives of cholesterol or its sterol precursors. They are generated from sterol metabolism and the interaction of cholesterol with REACTIVE OXYGEN SPECIES.	Oxysterol
D000074084	THP-1 Cells	A human leukemia monocytic cell line derived from a patient with LEUKEMIA, MONOCYTIC, ACUTE. It is used as a model to study the function of MONOCYTES and MACROPHAGES, their signaling pathways, nutrient and drug transport.	THP-1 Cell Line,Cell Line, THP-1,Cell Lines, THP-1,Cell, THP-1,Cells, THP-1,THP 1 Cell Line,THP 1 Cells,THP-1 Cell,THP-1 Cell Lines