MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN STIMULATES MONOCYTE ENDOTHELIAL INTERACTIONS
MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN STIMULATES MONOCYTE ENDOTHELIAL INTERACTIONS
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DOI：
10.1172/jci114562
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发表时间：
1990-04-01
影响因子：
15.9
通讯作者：
FOGELMAN, AM
中科院分区：
文献类型：
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作者：
BERLINER, JA;TERRITO, MC;FOGELMAN, AM
研究了最小修饰LDL （MM-LDL）对大血管内皮细胞（EC）与单核细胞和中性粒细胞相互作用能力的影响。这些低密度脂蛋白制剂，通过储存或轻度铁氧化获得，与天然低密度脂蛋白和低密度脂蛋白受体无法区分，并且不被清道夫受体识别。EC的处理少至0.12 .mu。g/ml MM-LDL导致单核细胞趋化因子的产生显著增加（7倍），单核细胞结合增加（3 - 5倍）。单核细胞结合在EC暴露于MM-LDL 4小时后达到最大，持续48小时，并被环己亚胺抑制。相比之下，暴露1-24 h后中性粒细胞结合没有增加。MM-LDL制剂的活性主要存在于极性脂质部分。MM-LDL对一只家兔的内皮细胞有毒性，但对另一只家兔或任何人脐静脉内皮细胞无毒性。耐药细胞在环己亚胺存在下与脂蛋白孵育时变得敏感，而敏感菌株在亚致死浓度的MM0-LDL预孵育时变得耐药。我们得出结论，EC暴露于亚致死水平的MM-LDL会增强单核细胞内皮相互作用，并诱导对MM-LDL毒性作用的抵抗。
The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 .mu.g/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM0-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL.