Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts.
Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts.
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DOI：
10.1371/journal.pone.0076893
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jancar S
中科院分区：
文献类型：
--
作者：
Rios FJ;Ferracini M;Pecenin M;Koga MM;Wang Y;Ketelhuth DF;Jancar S
巨噬细胞与氧化低密度脂蛋白（oxLDL）的相互作用导致其分化为泡沫细胞和细胞因子的产生，有助于动脉粥样硬化的发展。在以前的研究中，我们发现，CD 36和血小板活化因子受体（PAFR）是oxLDL激活细胞因子和CD 36基因转录所必需的。在这里，我们研究了CD 36和PAFR在oxLDL刺激的巨噬细胞中的定位和物理相互作用。我们发现阻断CD 36或PAFR可降低oxLDL摄取和IL-10产生。OxLDL仅在表达两种受体（PAFR和CD 36）的HEK 293 T中诱导IL-10 mRNA表达。OxLDL不诱导IL-12产生。β-CD破坏脂筏可降低oxLDL的摄取和IL-10的产生。OxLDL诱导PAFR和CD 36与组成性筏蛋白flotillin-1的免疫共沉淀，以及与脂筏标记物GM 1-神经节苷脂的共定位。最后，我们发现PAFR和CD 36在人动脉粥样硬化斑块的巨噬细胞中共定位。我们的研究结果表明，oxLDL诱导PAFR和CD 36募集到相同的脂筏，这是重要的oxLDL摄取和IL-10的生产。这项研究为oxLDL如何与巨噬细胞相互作用并促进动脉粥样硬化的发展提供了新的见解。
Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development.
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