Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide
Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide
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DOI：
10.1074/jbc.m313088200
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发表时间：
2004-07-23
影响因子：
4.8
通讯作者：
Ishibashi, S
中科院分区：
文献类型：
--
作者：
Tamura, Y;Osuga, J;Ishibashi, S
血管内皮细胞表达的清道夫受体I(SREC-I)是一种新型的乙酰化低密度脂蛋白(LDL)内源性受体。在这里，我们展示了SREC-I在多种组织中的表达，包括巨噬细胞和主动脉。脂多糖(LPS)强烈刺激巨噬细胞SREC-I的表达。为了阐明SREC-I在修饰的脂蛋白摄取和动脉粥样硬化发展中的作用，我们通过胚胎干细胞中的同源重组产生了SREC-I基因的靶向中断小鼠。为了排除A型清道夫受体(SR-A)对Ac-LDL摄取的压倒性影响，我们进一步通过杂交获得了同时缺乏SR-A和SREC-I(SR-A(-/-)；SREC-I-/-)的小鼠，并比较了分离的巨噬细胞对Ac-LDL的摄取和降解。在非刺激条件下，SR-A和SREC-I对Ac-LDL总降解率的贡献率分别为85%和5%。脂多糖使Ac-低密度脂蛋白的摄取和降解增加1.8倍。在此条件下，SR-A和SREC-I对Ac-LDL总降解率的贡献率分别为90%和6%。LP使SR-A和SREC-I的绝对贡献分别增加了1.9倍和2.3倍。另一方面，内毒素使其他途径的绝对贡献率降低了31%。一直以来，脂多糖不会增加清道夫受体家族其他成员的表达，如CD36。综上所述，在缺乏SR-A的内毒素刺激的巨噬细胞中，SREC-I是Ac-LDL的主要内吞受体，提示其与SR-A在动脉粥样硬化的发生发展中起着关键作用。
Scavenger receptor expressed by endothelial cells I (SREC-I) is a novel endocytic receptor for acetylated low density lipoprotein (LDL). Here we show that SREC-I is expressed in a wide variety of tissues, including macrophages and aortas. Lipopolysaccharide (LPS) robustly stimulated the expression of SREC-I in macrophages. In an initial attempt to clarify the role of SREC-I in the uptake of modified lipoproteins as well as in the development of atherosclerosis, we generated mice with a targeted disruption of the SREC-I gene by homologous recombination in embryonic stem cells. To exclude the overwhelming effect of the type A scavenger receptor (SR-A) on the uptake of Ac-LDL, we further generated mice lacking both SR-A and SREC-I (SR-A(-/-); SREC-I-/-) by cross-breeding and compared the uptake and degradation of Ac-LDL in the isolated macrophages. The contribution of SR-A and SREC-I to the overall degradation of Ac-LDL was 85 and 5%, respectively, in a non-stimulated condition. LPS increased the uptake and degradation of Ac-LDL by 1.8-fold. In this condition, the contribution of SR-A and SREC-I to the overall degradation of Ac-LDL was 90 and 6%, respectively. LPS increased the absolute contribution of SR-A and SREC-I by 1.9- and 2.3-fold, respectively. On the other hand, LPS decreased the absolute contribution of other pathways by 31%. Consistently, LPS did not increase the expression of other members of the scavenger receptor family such as CD36. In conclusion, SREC-I serves as a major endocytic receptor for Ac-LDL in LPS-stimulated macrophages lacking SR-A, suggesting that it has a key role in the development of atherosclerosis in concert with SR-A.