Phosphocholine as a pattern recognition ligand for CD36
Phosphocholine as a pattern recognition ligand for CD36
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DOI：
10.1194/jlr.m400496-jlr200
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发表时间：
2005-05-01
影响因子：
6.5
通讯作者：
Quehenberger, O
中科院分区：
文献类型：
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作者：
Boullier, A;Friedman, P;Quehenberger, O
我们之前已经证明，CD36 识别氧化 LDL (OxLDL) 上磷脂的氧化产物，例如 1-棕榈酰-2-(5'-氧代戊酰)-sn-甘油-3-磷酸胆碱 (POVPC)。目前的研究旨在检查 POVPC 中的磷酸胆碱 (PC) 头基是否构成 CD36 的强制性结合靶点。为了检查 PC 在 POVPC 与 CD36 结合中的作用，我们使用了与 BSA 或六肽交联的明确合成氧化磷脂 (OxPL)。然后测试OxPL加合物与CD36转染细胞结合的能力以及抑制OxLDL与CD36结合的能力。 POVPC-BSA 和 POVPC-肽加合物都是 CD36 的高亲和力配体和 OxLDL 结合的有效抑制剂。酶法去除POVPC-肽的整个PC部分，或单独去除胆碱头基，以及用乙醇胺取代胆碱头基，消除了POVPC的抑制活性。有趣的是，PC 本身或与 BSA 交联并没有表现出任何内在的竞争活动。总之，我们的数据表明，OxPL 的 PC 头基单独足以与 CD36 结合，但前提是以正确的构象存在，如 OxLDL 的 OxPL 或 POVPC-肽加合物。
We have previously shown that CD36 recognizes oxidation products of phospholipids on oxidized LDL ( OxLDL) such as 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine ( POVPC). The current study was designed to examine whether the phosphocholine (PC) headgroup in POVPC constitutes an obligatory binding target for CD36. To examine the contribution of PC in the binding of POVPC to CD36, we used well-defined synthetic oxidized phospholipids (OxPLs) cross-linked to BSA or to a hexapeptide. The OxPL adducts were then tested for their ability to bind to CD36-transfected cells and for their ability to inhibit OxLDL binding to CD36. Both POVPC-BSA and POVPC-peptide adducts were high-affinity ligands for CD36 and potent inhibitors of OxLDL binding. Enzymatic removal of the entire PC moiety of the POVPC-peptide, or of the choline headgroup alone, as well as substitution of the choline headgroup by ethanolamine abrogated the inhibitory activity of POVPC. Interestingly, PC by itself or cross-linked to BSA did not show any intrinsic competition activity. In conclusion, our data demonstrate that the PC headgroup of OxPL alone is sufficient for binding to CD36, but only if presented in the correct conformation as in OxPL of OxLDL or as in POVPC-peptide adducts.