Attenuated suppression of the oxidative burst by cells dying in the presence of oxidized low density lipoprotein

  • Macrophages ingesting apoptotic cells attenuate inflammatory responses, such as reactive oxygen species (ROS) generation. In atherosclerosis, ongoing inflammation and accumulation of apoptotic/necrotic material are observed, suggesting defects of phagocytes in recognizing or responding to dying cells. Modified lipoproteins such as oxidized LDL (oxLDL) are known to promote inflammation and to interfere with apoptotic cell clearance. Here, we studied the impact of cells exposed to oxLDL on their ability to interfere with the oxidative burst in phagocytes. In contrast to apoptotic cells, cells dying in response to or in the presence of oxLDL failed to suppress ROS generation despite efficiently being taken up by phagocytes. In addition, apoptotic cells, but not oxLDL-treated cells, inhibited phosphorylation of extracellular signal-regulated kinase, which is important for NADPH oxidase activation. oxLDL treatment did not interfere with activation of the antiinflammatory transcriptional regulator peroxisome proliferator-activated receptor gamma by apoptotic cells. Moreover, cells exposed to oxLDL failed to suppress lipopolysaccharide- induced proinflammatory cytokine expression, whereas apoptotic cells attenuated these phagocyte responses. Thus, the presence of oxLDL during cell death impaired the ability of apoptotic cells to act antiinflammatory with regard to oxidative burst inhibition and cytokine expression in phagocytes.

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Metadaten
Author:Dmitry NamgaladzeORCiD, Carla JenneweinGND, Stefan Preiss, Andreas von KnethenORCiDGND, Bernhard BrüneORCiD
URN:urn:nbn:de:hebis:30:3-764545
DOI:https://doi.org/https://doi.org/10.1194/jlr.M800615-JLR200
ISSN:0022-2275
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/19491397
Parent Title (English):Journal of lipid research
Publisher:American Society for Biochemistry and Molecular Biology Publications
Place of publication:Bethesda, Md
Document Type:Article
Language:English
Date of Publication (online):2021/01/04
Year of first Publication:2009
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/02/09
Tag:NADPH oxidase; apoptosis; lipoproteins; macrophages; phagocytosis; reactive oxygen species
Volume:50.2009
Issue:11
Page Number:9
First Page:2173
Last Page:2181
Institutes:Medizin
Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International