Membrane vesicles (MVs) released from activated cells and
blebs from apoptotic cells are increased in patients with
vascular disease and in those with atherosclerotic lesions, and their contribution to inflammatory reactions has been suggested. At sites of
inflammation, MVs could serve as rapidly available substrates for peroxidation, carry oxidized compounds to activate other cells, and amplify
inflammation. Here, we show that MVs released from
tert-butyl hydroperoxide-treated endothelial cells (ECs) and apoptotic
blebs, but not MVs from Ca(2+)
ionophore-treated ECs, stimulate monocyte adhesion to ECs, an important step in
atherogenesis. We show that oxidized
phospholipids, such as the previously identified
1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC), are responsible for
biological activity in MVs and apoptotic
blebs. Natural
antibodies from
apolipoprotein E-null mice that recognize POVPC also recognize oxidized MVs, and pretreatment of MVs with these
antibodies inhibits their ability to activate ECs. Furthermore, the
biological activity of oxidized MVs is inhibited by
platelet-activating factor receptor antagonists, which have been shown to inhibit the action of POVPC. Taken together, we show that oxidized MVs and apoptotic
blebs stimulate ECs to specifically bind monocytes, with oxidized
phospholipids (POVPC) being the active principle. In addition to oxidized
lipoproteins, oxidized MVs and apoptotic
blebs may play an important role in chronic inflammatory diseases, such as
atherosclerosis.