Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis
The liver is the central organ for cholesterol synthesis and homeostasis. The effects of dietary cholesterol on hepatic injury, mainly of oxidized low-density lipoproteins (OxLDL), are not fully understood. Here, we show that the degree of cholesterol oxidation had different impacts on the global ge...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.671073/full |
| _version_ | 1819138695082541056 |
|---|---|
| author | Ana C. Maretti-Mira Lucy Golden-Mason Matthew P. Salomon Mariana J. Kaplan Hugo R. Rosen |
| author_facet | Ana C. Maretti-Mira Lucy Golden-Mason Matthew P. Salomon Mariana J. Kaplan Hugo R. Rosen |
| author_sort | Ana C. Maretti-Mira |
| collection | DOAJ |
| description | The liver is the central organ for cholesterol synthesis and homeostasis. The effects of dietary cholesterol on hepatic injury, mainly of oxidized low-density lipoproteins (OxLDL), are not fully understood. Here, we show that the degree of cholesterol oxidation had different impacts on the global gene expression of human M2-like macrophages, with highly oxidized LDL causing the most dramatic changes. M2-like macrophages and Kupffer cells undergo M4-like polarization, decreasing the expression of important markers, such as IL10, MRC1, and CD163. These cells also displayed functional changes, with reduced phagocytic capacity, increased neutrophil recruitment, and more effective neutrophil extracellular traps (NETs) induction. Our findings provide a link between LDL oxidation and modification of peripheral and liver macrophage function. |
| first_indexed | 2024-12-22T11:10:51Z |
| format | Article |
| id | doaj.art-539b027499c24ba39f5ff4d0eb6988eb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T11:10:51Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-539b027499c24ba39f5ff4d0eb6988eb2022-12-21T18:28:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.671073671073Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosisAna C. Maretti-Mira0Lucy Golden-Mason1Matthew P. Salomon2Mariana J. Kaplan3Hugo R. Rosen4Department of Medicine, Keck School of Medicine, Gastroenterology & Hepatology, Research Center for Liver Disease, University of Southern California (USC), Los Angeles, CA, United StatesDepartment of Medicine, Keck School of Medicine, Gastroenterology & Hepatology, Research Center for Liver Disease, University of Southern California (USC), Los Angeles, CA, United StatesDepartment of Medicine, Keck School of Medicine, Gastroenterology & Hepatology, Research Center for Liver Disease, University of Southern California (USC), Los Angeles, CA, United StatesSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, United StatesDepartment of Medicine, Keck School of Medicine, Gastroenterology & Hepatology, Research Center for Liver Disease, University of Southern California (USC), Los Angeles, CA, United StatesThe liver is the central organ for cholesterol synthesis and homeostasis. The effects of dietary cholesterol on hepatic injury, mainly of oxidized low-density lipoproteins (OxLDL), are not fully understood. Here, we show that the degree of cholesterol oxidation had different impacts on the global gene expression of human M2-like macrophages, with highly oxidized LDL causing the most dramatic changes. M2-like macrophages and Kupffer cells undergo M4-like polarization, decreasing the expression of important markers, such as IL10, MRC1, and CD163. These cells also displayed functional changes, with reduced phagocytic capacity, increased neutrophil recruitment, and more effective neutrophil extracellular traps (NETs) induction. Our findings provide a link between LDL oxidation and modification of peripheral and liver macrophage function.https://www.frontiersin.org/articles/10.3389/fimmu.2021.671073/fullmacrophagesKupffer cellsliverlow-density lipoprotein (LDL)non-alcoholic steatohepatitis (NASH)neutrophil |
| spellingShingle | Ana C. Maretti-Mira Lucy Golden-Mason Matthew P. Salomon Mariana J. Kaplan Hugo R. Rosen Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis Frontiers in Immunology macrophages Kupffer cells liver low-density lipoprotein (LDL) non-alcoholic steatohepatitis (NASH) neutrophil |
| title | Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis |
| title_full | Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis |
| title_fullStr | Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis |
| title_full_unstemmed | Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis |
| title_short | Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis |
| title_sort | cholesterol induced m4 like macrophages recruit neutrophils and induce netosis |
| topic | macrophages Kupffer cells liver low-density lipoprotein (LDL) non-alcoholic steatohepatitis (NASH) neutrophil |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.671073/full |
| work_keys_str_mv | AT anacmarettimira cholesterolinducedm4likemacrophagesrecruitneutrophilsandinducenetosis AT lucygoldenmason cholesterolinducedm4likemacrophagesrecruitneutrophilsandinducenetosis AT matthewpsalomon cholesterolinducedm4likemacrophagesrecruitneutrophilsandinducenetosis AT marianajkaplan cholesterolinducedm4likemacrophagesrecruitneutrophilsandinducenetosis AT hugorrosen cholesterolinducedm4likemacrophagesrecruitneutrophilsandinducenetosis |