LIPOPOLYSACCHARIDE STIMULATION OF RAW 264.7 MACROPHAGES INDUCES LIPID-ACCUMULATION AND FOAM CELL-FORMATION
LIPOPOLYSACCHARIDE STIMULATION OF RAW 264.7 MACROPHAGES INDUCES LIPID-ACCUMULATION AND FOAM CELL-FORMATION
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DOI：
10.1016/0021-9150(93)90224-i
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发表时间：
1993-01-04
期刊：
影响因子：
5.3
通讯作者：
GRUNFELD, C
中科院分区：
文献类型：
--
作者：
FUNK, JL;FEINGOLD, KR;GRUNFELD, C
免疫和炎症过程在诱导动脉粥样硬化病变中的作用正在显现。进行这些研究以确定脂多糖（LPS）激活是否增强巨噬细胞变成泡沫细胞的能力。由于LPS激活抑制清道夫受体活性，我们研究了LPS激活的RAW 264.7巨噬细胞从各种脂质颗粒中积累脂质的能力，这些脂质颗粒不是清道夫受体的配体。在没有脂质颗粒的情况下，LPS激活的巨噬细胞积累甘油三酯，但不积累胆固醇酯（CE）。添加富含甘油三酯的颗粒Apricacal进一步增强了这种LPS刺激的甘油三酯积累。与对照组相比，LPS激活同样增强了两种富含CE的脂蛋白（β VLDL和LDL）的CE积累近3倍。未受刺激的对照细胞仅从β VLDL而不是LDL积累显著的CE。LPS增强的脂质积累依赖于LPS剂量，并在孵育8-12小时后开始。LPS使I-125标记的LDL和细胞相关的I-125标记的LDL在37 ℃下的降解增加了1.8倍。降解保持饱和，与受体介导的过程一致。抗氧化剂不抑制LPS诱导的LDL中CE的积累。因此，RAW 264.7巨噬细胞的活化增强了它们从各种脂质颗粒中积累脂质并成为泡沫细胞的能力。这些数据表明，感染，特别是LPS在动脉粥样硬化形成中的潜在作用。
A role for immune and inflammatory processes in the induction of atherosclerotic lesions is emerging. These studies were undertaken to determine whether activation by lipopolysaccharide (LPS) enhances the ability of macrophages to become foam cells. Since LPS activation inhibits scavenger receptor activity, we studied the ability of LPS-activated RAW 264.7 macrophages to accumulate lipid from a variety of lipid particles that are not ligands for the scavenger receptor. Macrophages activated by LPS, in the absence of lipid particles, accumulated triglyceride, but not cholesterol ester (CE). The addition of Soyacal, a triglyceride-rich particle, further enhanced this LPS-stimulated triglyceride accumulation. LPS activation similarly enhanced CE accumulation almost 3-fold from two CE-rich lipoproteins, betaVLDL and LDL, as compared with controls. The unstimulated control cells only accumulated significant CE from betaVLDL and not LDL. LPS-enhanced lipid accumulation was dependent on LPS dose and began after 8-12 h of incubation. LPS increased the degradation of I-125-labelled LDL and the cell-associated I-125-labelled LDL at 37-degrees-C by 1.8-fold. Degradation remained saturable, consistent with a receptor-mediated process. Antioxidants did not inhibit LPS-induced CE accumulation from LDL. Thus, activation of RAW 264.7 macrophages enhanced their ability to accumulate lipid from a variety of lipid particles and to become foam cells. These data suggest a potential role for infections, and LPS in particular, in atherogenesis.