Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions
Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions
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DOI：
10.1161/hq0102.101525
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发表时间：
2002-01-01
影响因子：
8.7
通讯作者：
Leitinger, N
中科院分区：
文献类型：
--
作者：
Huber, J;Vales, A;Leitinger, N
在血管疾病患者和动脉粥样硬化病变患者中，活化细胞释放的膜囊泡（MV）和凋亡细胞释放的水泡增加，并已表明它们对炎症反应的贡献。在炎症部位。MV可以作为快速可用的过氧化底物，携带氧化化合物激活其他细胞，并放大炎症。在这里，我们表明，MV释放叔丁基过氧化氢处理的内皮细胞（EC）和凋亡的水泡，但不是MV从钙离子载体处理的EC，刺激单核细胞粘附到EC，动脉粥样硬化的重要步骤。我们发现，氧化磷脂，如以前确定的1-棕榈酰-2-（5-oxovaleroyl）-sn-甘油-3-磷酸胆碱（POVPC），是负责MV和凋亡水泡的生物活性。来自载脂蛋白E缺失小鼠的识别POVPC的天然抗体也识别氧化的MV，并且用这些抗体预处理MV抑制其激活EC的能力。此外，氧化MV的生物活性被血小板活化因子受体拮抗剂抑制，这些拮抗剂已显示出抑制POVPC的作用。两者合计，我们表明，氧化MV和凋亡水泡刺激EC特异性结合单核细胞，氧化磷脂（POVPC）的活性成分。除氧化脂蛋白外，氧化MV和凋亡泡可能在慢性炎症性疾病如动脉粥样硬化中起重要作用。
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.