Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein.
Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein.
复制标题
内皮细胞源性对小鼠腹腔巨噬细胞的趋化活性以及低密度脂蛋白修饰形式的影响。
DOI：
10.1073/pnas.82.17.5949
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发表时间：
1985
影响因子：
11.1
通讯作者：
Steinberg,D
中科院分区：
文献类型：
--
作者：
Quinn,MT;Parthasarathy,S;Steinberg,D
培养的兔和牛主动脉内皮细胞对小鼠腹腔巨噬细胞产生趋化活性，在条件培养基中可证实。该趋化活性是热稳定的，并且未提取到氯仿/甲醇中。通过添加内皮细胞修饰的低密度脂蛋白（EC修饰的LDL）可抑制该作用，该LDL是一种先前显示含有过氧化脂质、增加的溶血磷脂酰胆碱和部分降解的载脂蛋白B的LDL形式。趋化活性也被抑制LDL预先氧化的细胞与5 μ M的Cu 2+的情况下。抑制活性存在于EC修饰的LDL的脂质提取物中，但不存在于天然LDL中，推测代表过氧化脂质成分。EC修饰的LDL也抑制酵母多糖激活血清的趋化活性。由于EC修饰的LDL部分通过乙酰-LDL受体摄取，因此测试了乙酰-LDL的作用。而不是抑制趋化性，乙酰低密度脂蛋白表现出内在的积极的趋化活性也岩藻多糖和聚肌胞，这两者也与乙酰-LDL受体相互作用。这些研究表明，巨噬细胞可能通过内皮细胞衍生的趋化因子或结构上与岩藻多糖或聚肌苷酸相关的天然聚阴离子被招募到内皮下空间中，然后由于修饰形式的LDL中过氧化脂质成分的抑制作用而被“捕获”在那里的机制。
Cultured rabbit and bovine aortic endothelial cells generated chemotactic activity for mouse resident peritoneal macrophages, demonstrable in the conditioned medium. This chemotactic activity was heat stable and was not extracted into chloroform/methanol. It was inhibited by addition of endothelial cell-modified low density lipoprotein (EC-modified LDL), a form of LDL shown previously to contain peroxidized lipids, increased lysophosphatidylcholine, and partially degraded apoprotein B. The chemotactic activity was also inhibited by LDL previously oxidized in the absence of cells with 5 microM Cu2+. Inhibitory activity was present in the lipid extract of EC-modified LDL but not in that of native LDL, presumably representing peroxidized lipid components. EC-modified LDL also inhibited the chemotactic activity of zymosan-activated serum. Because EC-modified LDL is taken up in part by way of the acetyl-LDL receptor, the effects of acetyl-LDL were tested. Rather than inhibiting chemotaxis, acetyl LDL showed intrinsic positive chemotactic activity as did also fucoidin and polyinosinic acid, both of which also interact with the acetyl-LDL receptor. These studies suggest mechanisms by which macrophages may be recruited into the subendothelial space by endothelial cell-derived chemotactic factors or by natural polyanions structurally related to fucoidin or polyinosinic acid and then become "trapped" there because of the inhibitory effects of peroxidized lipid components in modified forms of LDL.