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.