Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies |
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Authors: | Dimitrios Tsiantoulas Thomas Perkmann Taras Afonyushkin Andreas Mangold Thomas A Prohaska Nikolina Papac-Milicevic Vincent Millischer Caroline Bartel Sohvi H?rkk? Chantal M Boulanger Sotirios Tsimikas Michael B Fischer Joseph L Witztum Irene M Lang Christoph J Binder |
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Institution: | 112. Department of Blood Group Serology Transfusion Medicine, Medical University of Vienna, Vienna, Austria;2. Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria;4. Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems, Austria;11. Medical Research Center and Department of Medical Microbiology and Immunology, Institute of Diagnostics, University of Oulu, Oulu, Finland;8. INSERM U970, Paris Cardiovascular Research Center - PARCC, Paris, France |
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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. |
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Keywords: | immunoglobulin M antibodies malondialdehyde acute coronary syndrome |
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