title: Oxidation-specific epitopes are major targets of innate immunity in atherothrombosis.
abstract: Atherosclerosis is a chronic inflammatory disease of the vascular wall that results from disturbed lipoprotein metabolism and increased oxidative stress. A major consequence of this is lipid peroxidation, which generates a number of breakdown products of membrane lipids that form so called oxidation-specific epitopes (OSE). OSE have been documented in oxidized lipoproteins and on the surface of dying cells and circulating microparticles, and their ability to trigger robust pro-inflammatory and pro-thrombotic responses has been demonstrated extensively. Recent studies have identified specific OSE as major targets of both cellular and soluble pattern recognition receptors of the innate immune system, including innate natural IgM antibodies. This allows the immune system to identify metabolic waste and mediate important physiological house keeping functions, e.g. by promoting the removal of cellular debris and by neutralizing oxidized molecules. Indeed, innate B1 cells and B1 cell derived natural IgM with specificity for OSE have been shown to protect mice from the development of atherosclerotic lesions. Moreover, OSE-specific natural IgM antibodies bind and neutralize the pro-inflammatory and pro-thrombotic effects of OSE, and low levels of OSE-specific IgM are associated with an increased risk for myocardial infarction.
  
  
  CONCLUSIONS
  Understanding the molecular components and mechanisms involved in this process, will help identify individuals with increased risk for atherothrombosis and indicate novel points for therapeutic intervention.
authors: Barbara
authors: B
authors: Bartolini Gritti
authors: Christoph J. Binder, MD, PhD, Dept. of Laboratory Medicine & CeMM, Lazarettgasse 14, AKH BT 25/2, 1090 Vienna, Austria, Tel. +43/1/404 00 73-755, Fax -566, E-mail: christoph.binder@meduniwien.ac.at.
authors: Christoph J
authors: CJ
authors: Binder
mesh_terms: D000818:Animals; D001158:Arteries / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D019317:Evidence-Based Medicine; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D050356:Lipid Metabolism / Q000276:immunology*; D018448:Models, Immunological; D018384:Oxidative Stress / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology
chemical_list: D016207:Cytokines; D000939:Epitopes; D007155:Immunologic Factors; D017382:Reactive Oxygen Species
keywords: Atherothrombosis; innate immunity; natural IgM antibodies; oxidized LDL