The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the lipoprotein
The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the lipoprotein
复制标题
DOI：
10.1074/jbc.275.13.9163
复制
发表时间：
2000-03-31
影响因子：
4.8
通讯作者：
Quehenberger, O
中科院分区：
文献类型：
--
作者：
Boullier, A;Gillotte, KL;Quehenberger, O
越来越多的证据表明，CD36在巨噬细胞摄取氧化低密度脂蛋白(OxLDL)中具有重要的生理功能，然而，介导其与CD36结合的配体特异性和配体的性质仍不明确，最近的研究结果表明，参与OxLDL摄取的一些巨噬细胞清道夫受体既识别OxLDL的脂类部分，也识别其蛋白质部分，但没有确凿的直接证据。本研究旨在检测单一的、具有良好特性的OzLDL受体CD36是否能与瞬时转染小鼠CD36的完整OxLDL结合的COS-7细胞的脂质和蛋白质部分结合。由OxLDL重组的apoB和OxLDL脂类制备的微乳都非常有效地抑制了这种结合(类似于50%)。通过直接配基结合分析和相互抑制进一步证实了这两个部分与CD36的特异性结合，即OxLDL的apoB抑制了OxLDL脂类的结合，反之亦然。此外，一种识别氧化低密度脂蛋白氧化特异性表位的单抗抑制了完整氧化低密度脂蛋白及其纯化的蛋白和脂类部分与CD36的结合，该抗体识别磷脂L-棕榈酰基-2-(5‘-氧代戊酰基)磷脂酰胆碱，这种氧化磷脂模型也是氧化低密度脂蛋白与CD36结合的有效竞争者。我们的结果表明，脂相中氧化的磷脂或与载脂蛋白B共价连接的磷脂作为CD36识别的配体，至少部分地介导了氧化低密度脂蛋白与巨噬细胞的高亲和力。
There is growing evidence that CD36 has an important physiological function in the uptake of oxidized low density lipoprotein (OxLDL) by macrophages, However, the ligand specificity and the nature of the ligands on OxLDL that mediate the binding to CD36 remain ill defined, Results from recent studies suggested that some of the macrophage scavenger receptors involved in the uptake of OxLDL recognized both the lipid and the protein moieties of OxLDL, but there was no conclusive direct evidence for this. The present studies were undertaken to test whether a single, well characterized OzLDL receptor, CD36, could bind both the lipid and protein moieties of OxLDL, COS-7 cells transiently transfected with mouse CD36 cDNA bound intact OxLDL with high affinity. This binding was very effectively inhibited (similar to 50%) both by the reconstituted apoB from OxLDL and by microemulsions prepared from OxLDL lipids. The specific binding of both moieties to CD36 was further confirmed by direct ligand binding analysis and by demonstrating reciprocal inhibition, i.e. apoB from OxLDL inhibited the binding of the OxLDL lipids and vice versa. Furthermore, a monoclonal mouse antibody that recognizes oxidation-specific epitopes in OxLDL inhibited the binding of intact OxLDL and also that of its purified protein and lipid moieties to CD36, This antibody recognizes the phospholipid l-palmitoyl 2-(5'-oxovaleroyl) phosphatidylcholine, This model of an oxidized phospholipid was also an effective competitor for the CD36 binding of both the resolubilized apoB and the lipid microemulsions from OxLDL, Our results demonstrate that oxidized phospholipids in the lipid phase or covalently attached to apoB serve as ligands for recognition by CD36 and, at least in part, mediate the high affinity binding of OxLDL to macrophages.