doi: 10.1161/hq0102.101525
© 2002 American Heart Association, Inc.
Vascular Biology |
Oxidized Membrane Vesicles and Blebs From Apoptotic Cells Contain Biologically Active Oxidized Phospholipids That Induce Monocyte-Endothelial Interactions
From the Department of Vascular Biology and Thrombosis Research (J.H., A.V., B.R.B., N.L.), University of Vienna; the Clinical Institute of Medical and Chemical Laboratory Analysis (G.M., R.S.), General Hospital Vienna; and the Department of Zoology (M.B.), University of Vienna, Vienna, Austria; and the Department of Medicine (J.L.W.), University of California, San Diego.
Correspondence to Dr Norbert Leitinger, Department of Vascular Biology and Thrombosis Research, University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. E-mail norbert.leitinger{at}univie.ac.at
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 Ca2+ 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.
Key Words: membrane vesicles • apoptotic blebs • oxidized phospholipids • endothelial cells • atherosclerosis
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