title: Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies.
abstract: Oxidation-specific epitopes (OSEs) present on apoptotic cells and oxidized low density lipoprotein (OxLDL) represent danger-associated molecular patterns that are recognized by different arcs of innate immunity, including natural IgM antibodies. Here, we investigated whether circulating microparticles (MPs), which are small membrane vesicles released by apoptotic or activated cells, are physiological carriers of OSEs. OSEs on circulating MPs isolated from healthy donors and patients with ST-segment elevation myocardial infarction (STE-MI) were characterized by flow cytometry using a panel of OSE-specific monoclonal antibodies. We found that a subset of MPs carry OSEs on their surface, predominantly malondialdehyde (MDA) epitopes. Consistent with this, a majority of IgM antibodies bound on the surface of circulating MPs were found to have specificity for MDA-modified LDL. Moreover, we show that MPs can stimulate THP-1 (human acute monocytic leukemia cell line) and human primary monocytes to produce interleukin 8, which can be inhibited by a monoclonal IgM with specificity for MDA epitopes. Finally, we show that MDA(+) MPs are elevated at the culprit lesion site of patients with STE-MI. Our results identify a subset of OSE(+) MPs that are bound by OxLDL-specific IgM. These findings demonstrate a novel mechanism by which anti-OxLDL IgM antibodies could mediate protective functions in CVD.
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems, Austria.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsiantoulas
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Taras
authors.initials: T
authors.lastname: Afonyushkin
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mangold
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Prohaska
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Papac-Milicevic
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Vincent
authors.initials: V
authors.lastname: Millischer
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bartel
authors.affiliation: Medical Research Center and Department of Medical Microbiology and Immunology, Institute of Diagnostics, University of Oulu, Oulu, Finland.
authors.forename: Sohvi
authors.initials: S
authors.lastname: Hörkkö
authors.affiliation: INSERM U970, Paris Cardiovascular Research Center - PARCC, Paris, France.
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Boulanger
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
authors.affiliation: Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems, Austria Department of Blood Group Serology Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fischer
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems, Austria.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology / Q000378:metabolism; D000328:Adult; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D000939:Epitopes; D007075:Immunoglobulin M; D008315:Malondialdehyde
keywords: acute coronary syndrome; immunoglobulin M antibodies; malondialdehyde