Phospholipids in oxidized LDL not adducted to apoB are recognized by the CD36 scavenger receptor
Phospholipids in oxidized LDL not adducted to apoB are recognized by the CD36 scavenger receptor
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DOI：
10.1016/s0891-5849(02)01294-7
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发表时间：
2003-02-01
影响因子：
7.4
通讯作者：
Hoff, HF
中科院分区：
文献类型：
--
作者：
Podrez, EA;Hoppe, G;Hoff, HF
先前的研究表明，低密度脂蛋白（oxLDL）的氧化导致其被巨噬细胞上的清道夫受体识别。虽然脂质过氧化产物对 oxLDL apoB-100 上赖氨酰残基的阻断似乎对于 A 类清道夫受体 (SR-A) 的识别至关重要，但脂质部分的修饰已被认为是 B 类清道夫受体 CD36 识别的关键。我们研究了氧化 LDL 的清道夫受体的识别，其中赖氨酰残基在氧化之前通过甲基化 [ox(m)LDL] 被阻断。这使我们能够最大限度地减少修饰的 apoB-100 对 oxLDL 识别的贡献，但不会破坏颗粒中脂质的天然构型。我们发现 ox(m)LDL 几乎与 oxLDL 一样被小鼠腹膜巨噬细胞 (MPM) 上的受体识别。 Ox(m)LDL 可以被 CD36 转染的细胞识别，但不能被 SR-A 转染的细胞识别。氧化磷脂 (oxPC) 从 oxLDL 转移或直接从 oxPC 转移到 LDL，通过 CD36 转染细胞进行识别，证实 CD36 识别 ox(m)LDL 中未结合的氧化磷脂。总的来说，这些结果表明，完整 oxLDL 颗粒内未加合到 apoB 的 oxPC 被巨噬细胞清道夫受体 CD36 识别，这些脂质不被 SR-A 识别，并且它们可以从氧化 LDL 转移到未氧化 LDL 并诱导 CD36 识别。 (C) 2003 爱思唯尔科学公司。
Previous studies have shown that oxidation of low-density lipoprotein (oxLDL) results in its recognition by scavenger receptors on macrophages. Whereas blockage of lysyl residues on apoB-100 of oxLDL by lipid peroxidation products appears to be critical for recognition by the scavenger receptor class A (SR-A), modification of the lipid moiety has been suggested to be responsible for recognition by the scavenger class B receptor, CD36. We studied the recognition by scavenger receptors of oxidized LDL in which lysyl residues are blocked prior to oxidation through methylation [ox(m)LDL]. This permits us to minimize any contribution of modified apoB-100 to the recognition of oxLDL, but does not disrupt the native configuration of lipids in the particle. We found that ox(m)LDL was recognized by receptors on mouse peritoneal macrophages (MPM) almost as well as oxLDL. Ox(m)LDL was recognized by CD36-transfected cells but not by SR-A-transfected cells. Oxidized phospholipids (oxPC) transferred from oxLDL or directly from oxPC to LDL, conveyed recognition by CD36-transfected cells, confirming that CD36 recognized unbound oxidized phospholipids in ox(m)LDL. Collectively, these results suggest that oxPC not adducted to apoB within the intact oxLDL particle are recognized by the macrophage scavenger receptor CD36, that these lipids are not recognized by SR-A, and that they can transfer from oxidized to unoxidized LDL and induce CD36 recognition. (C) 2003 Elsevier Science Inc.