Scavenger Receptor Expressed by Endothelial Cells I (SREC-I) Mediates the Uptake of Acetylated Low Density Lipoproteins by Macrophages Stimulated with Lipopolysaccharide
Copyright policy )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) 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.
- University of Tsukuba Japan
- Obihiro University of Agriculture and Veterinary Medicine Japan
- University of Tokyo Japan
- RIKEN Japan
CD36 Antigens, Lipopolysaccharides, Mice, Knockout, Base Sequence, Arteriosclerosis, Macrophages, Molecular Sequence Data, Biological Transport, Active, Gene Expression, Endocytosis, Lipoproteins, LDL, Mice, Inbred C57BL, Mice, Macrophages, Peritoneal, Animals, Amino Acid Sequence, RNA, Messenger, Cell Adhesion Molecules, Aorta, DNA Primers
CD36 Antigens, Lipopolysaccharides, Mice, Knockout, Base Sequence, Arteriosclerosis, Macrophages, Molecular Sequence Data, Biological Transport, Active, Gene Expression, Endocytosis, Lipoproteins, LDL, Mice, Inbred C57BL, Mice, Macrophages, Peritoneal, Animals, Amino Acid Sequence, RNA, Messenger, Cell Adhesion Molecules, Aorta, DNA Primers
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