Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies

Publikationen: Beitrag in FachzeitschriftArtikelForschung(peer-reviewed)

Autoren

  • Dimitrios Tsiantoulas
  • Thomas Perkmann
  • Taras Afonyushkin
  • Andreas Mangold
  • Nikolina Papac-Milicevic
  • Vincent Millischer
  • Caroline Bartel
  • Sohvi Hörkkö
  • Chantal M. Boulanger
  • Sotirios Tsimikas
  • Michael B. Fischer
  • Joseph L. Witztum
  • Irene M. Lang

Externe Organisationseinheiten

  • Medizinische Universität Wien
  • Paris Cardiovascular Research Center - PARCC
  • University of California, San Diego
  • Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems
  • Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)440-448
Seitenumfang9
FachzeitschriftJournal of lipid research
Jahrgang56.2015
Ausgabenummer2
Frühes Online-Datum18 Dez. 2014
DOIs
StatusVeröffentlicht - Feb. 2015