Endothelial lipase modulates monocyte adhesion to the vessel wall - A potential role in inflammation
Endothelial lipase modulates monocyte adhesion to the vessel wall - A potential role in inflammation
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DOI：
10.1074/jbc.m411112200
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发表时间：
2004-12-24
影响因子：
4.8
通讯作者：
Yokoyama, M
中科院分区：
文献类型：
--
作者：
Kojma, Y;Hirata, K;Yokoyama, M
内皮脂肪酶(EL)是脂蛋白脂酶基因家族的新成员，在高密度脂蛋白代谢中起着核心作用。以往的研究表明，在人类冠状动脉粥样硬化病变中，EL表达于内皮细胞、巨噬细胞和平滑肌细胞。然而，EL在局部血管壁中的功能作用仍不清楚。在这项研究中，我们评估了EL调节单核细胞与内皮细胞表面黏附的能力。内毒素致炎小鼠组织中EL基因和蛋白水平显著升高。体外黏附实验表明，EL在COS7或PRO5细胞中的过表达增强了单核细胞与EL表达细胞的结合。肝素或肝素酶处理以剂量依赖的方式抑制EL介导的单核细胞黏附增加。体外黏附实验显示，与野生型小鼠相比，EL转基因小鼠主动脉条上的黏附单核细胞数显著增加，而EL基因敲除小鼠的黏附单核细胞数明显减少。这些结果提示，内皮细胞表面的EL可通过与硫酸乙酰肝素蛋白多糖相互作用促进单核细胞与血管内皮细胞的黏附。因此，炎症刺激上调EL可能参与了炎症的发展。
Endothelial lipase (EL), a new member of the lipoprotein lipase gene family, plays a central role in high density lipoprotein metabolism. Previous studies indicated that EL is expressed in endothelial cells, macrophages, and smooth muscle cells in atherosclerotic lesions in human coronary arteries. However, the functional role of EL in the local vessel wall remains obscure. In this study, we evaluated the ability of EL to modulate monocyte adhesion to the endothelial cell surface. EL mRNA and protein levels were markedly increased in tissues of the mouse model of inflammation induced by lipopolysaccharide injection. Adhesion assays in vitro revealed that overexpression of EL in COS7 or Pro5 cells enhanced monocyte bindings to the EL-expression cells. Heparin or heparinase treatment inhibited EL-mediated increases of monocyte adhesion in a dose-dependent manner. Moreover, ex vivo adhesion assays revealed that the number of adherent monocytes on aortic strips was significantly increased in EL transgenic mice and decreased in EL knock-out mice as compared with wildtype mice. These results suggest that EL on the endothelial cell surface can promote monocyte adhesion to the vascular endothelium through the interaction with heparan sulfate proteoglycans. Thus, the up-regulation of EL by inflammatory stimuli may be involved in the progression of inflammation.