MONOCYTE TRANSMIGRATION INDUCED BY MODIFICATION OF LOW-DENSITY-LIPOPROTEIN IN COCULTURES OF HUMAN AORTIC-WALL CELLS IS DUE TO INDUCTION OF MONOCYTE CHEMOTACTIC PROTEIN-1 SYNTHESIS AND IS ABOLISHED BY HIGH-DENSITY-LIPOPROTEIN
MONOCYTE TRANSMIGRATION INDUCED BY MODIFICATION OF LOW-DENSITY-LIPOPROTEIN IN COCULTURES OF HUMAN AORTIC-WALL CELLS IS DUE TO INDUCTION OF MONOCYTE CHEMOTACTIC PROTEIN-1 SYNTHESIS AND IS ABOLISHED BY HIGH-DENSITY-LIPOPROTEIN
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DOI：
10.1172/jci115532
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发表时间：
1991-12-01
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：
NAVAB, M;IMES, SS;FOGELMAN, AM
人主动脉内皮细胞（HAEC）和平滑肌细胞（HASMC）与LDL在5-10%人血清存在下的共培养物的孵育导致单核细胞趋化蛋白1（MCP-1）mRNA的7.2倍诱导，共培养物上清液中MCP-1蛋白水平的2.5倍增加，单核细胞迁移到共培养物的内皮下空间中增加了7.1倍。单核细胞迁移被MCP-1抗体抑制91%。从与LDL孵育的共培养物中收集的培养基诱导靶内皮细胞（EC）结合单核细胞，但不结合嗜中性粒细胞样细胞。从与LDL诱导的单核细胞迁移到未暴露于LDL的其他共培养物的内皮下空间中孵育的共培养物中收集的培养基。相比之下，来自EC或平滑肌细胞（SMC）的单独培养物的培养基与共培养物相比含有相同数量的EC或SMC，并且与相同的LDL孵育，当与靶共培养物孵育时，不诱导单核细胞迁移。高密度脂蛋白HDL，当与LDL一起共培养时，减少了91%的单核细胞迁移增加。几乎所有HDL介导的抑制都是由HDL 2亚组分引起的。HDL 3基本上没有影响。载脂蛋白A1也是无效的，在防止单核细胞的迁移，而磷脂酰胆碱脂质体是有效的HDL 2表明，HDL 2的脂质成分可能是负责其行动。用β-胡萝卜素或α-生育酚预孵育LDL并不能减少单核细胞迁移。然而，用普罗布考预处理LDL或在加入LDL之前用普罗布考、β-胡萝卜素或α-生育酚预处理共培养物阻止LDL诱导的单核细胞迁移。在暴露于共培养物后，向LDL中添加HDL或普罗布考并不能阻止修饰的LDL诱导新鲜共培养物中的单核细胞迁移。我们的结论是，人主动脉细胞的共培养物可以修改LDL，即使在血清的存在下，导致MCP-1的诱导，和HDL和抗氧化剂防止LDL诱导的单核细胞迁移。
Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to co-culture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein Al was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration.