Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1994 Nov 15;304(Pt 1):69–73. doi: 10.1042/bj3040069

Binding characteristics of scavenger receptors on liver endothelial and Kupffer cells for modified low-density lipoproteins.

Y B De Rijke 1, E A Biessen 1, C J Vogelezang 1, T J van Berkel 1
PMCID: PMC1137453  PMID: 7998959

Abstract

Previous studies showed that both endothelial and Kupffer cells contain specific recognition sites of oxidized low-density lipoprotein (OxLDL), in addition to recognition sites which recognize OxLDL and acetylated LDL (AcLDL). We have determined the binding characteristics of the recognition sites for OxLDL on Kupffer cells and endothelial cells (OxLDL-specific binding-site) in comparison to the recognition site for AcLDL on endothelial cells, which recognizes both AcLDL and OxLDL (Ac/OxLDL binding site). The capacity of Kupffer cells to bind OxLDL (Bmax. = 779 ng of 125I-OxLDL/mg of cell protein; Kd = 6 micrograms/ml) was comparable to the binding-capacity of endothelial cells (Bmax. = 803 ng of 125I-OxLDL/mg of cell protein; Kd = 5 micrograms/ml). The effect of net charge of modified LDL on its affinity for the recognition sites on Kupffer and endothelial cells was evaluated using competition studies. The affinity of AcLDL for the Ac/OxLDL binding site was greatly increased from 460 micrograms/ml to 4 micrograms/ml with increasing extent of modification and thus net charge. The Ac/OxLDL binding-site on endothelial cells also displayed an increased affinity towards LDL with an increasing degree of oxidation. The affinity of OxLDL for the Ac/OxLDL binding-site appeared to be about 4-fold higher than that of AcLDL with a similar extent of modification. At higher degrees of oxidation of LDL, the affinity for the OxLDL-specific site on endothelial and Kupffer cells was also strongly enhanced; the OxLDL-specific binding-site possesses a higher affinity for mildly oxidized LDL as compared with the Ac/OxLDL binding-site. It is concluded that recognition of OxLDL by both the OxLDL-specific binding-site and the Ac/OxLDL binding-site on liver endothelial and Kupffer cells depends on the net negative charge of modified LDL. The similarity in binding pattern of these binding sites makes it likely that the newly described 95 kD OxLDL binding protein on Kupffer cells [Y. B. De Rijke and Th. J. C. van Berkel, J. Biol. Chem. (1994), 269, 824-827] contains a recognition site with similar structural elements as described earlier for scavenger receptors.

Full text

PDF
69

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acton S., Resnick D., Freeman M., Ekkel Y., Ashkenas J., Krieger M. The collagenous domains of macrophage scavenger receptors and complement component C1q mediate their similar, but not identical, binding specificities for polyanionic ligands. J Biol Chem. 1993 Feb 15;268(5):3530–3537. [PubMed] [Google Scholar]
  2. Basu S. K., Goldstein J. L., Anderson G. W., Brown M. S. Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3178–3182. doi: 10.1073/pnas.73.9.3178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  4. Brown M. S., Basu S. K., Falck J. R., Ho Y. K., Goldstein J. L. The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages. J Supramol Struct. 1980;13(1):67–81. doi: 10.1002/jss.400130107. [DOI] [PubMed] [Google Scholar]
  5. Chen S. H., Yang C. Y., Chen P. F., Setzer D., Tanimura M., Li W. H., Gotto A. M., Jr, Chan L. The complete cDNA and amino acid sequence of human apolipoprotein B-100. J Biol Chem. 1986 Oct 5;261(28):12918–12921. [PubMed] [Google Scholar]
  6. Doi T., Higashino K., Kurihara Y., Wada Y., Miyazaki T., Nakamura H., Uesugi S., Imanishi T., Kawabe Y., Itakura H. Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors. J Biol Chem. 1993 Jan 25;268(3):2126–2133. [PubMed] [Google Scholar]
  7. Fogelman A. M., Shechter I., Seager J., Hokom M., Child J. S., Edwards P. A. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2214–2218. doi: 10.1073/pnas.77.4.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldstein J. L., Ho Y. K., Basu S. K., Brown M. S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979 Jan;76(1):333–337. doi: 10.1073/pnas.76.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Habeeb A. F. Determination of free amino groups in proteins by trinitrobenzenesulfonic acid. Anal Biochem. 1966 Mar;14(3):328–336. doi: 10.1016/0003-2697(66)90275-2. [DOI] [PubMed] [Google Scholar]
  10. Haberland M. E., Fogelman A. M., Edwards P. A. Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1712–1716. doi: 10.1073/pnas.79.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jansen R. W., Kruijt J. K., van Berkel T. J., Meijer D. K. Coupling of the antiviral drug ara-AMP to lactosaminated albumin leads to specific uptake in rat and human hepatocytes. Hepatology. 1993 Jul;18(1):146–152. [PubMed] [Google Scholar]
  12. Kodama T., Freeman M., Rohrer L., Zabrecky J., Matsudaira P., Krieger M. Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature. 1990 Feb 8;343(6258):531–535. doi: 10.1038/343531a0. [DOI] [PubMed] [Google Scholar]
  13. McFARLANE A. S. Efficient trace-labelling of proteins with iodine. Nature. 1958 Jul 5;182(4627):53–53. doi: 10.1038/182053a0. [DOI] [PubMed] [Google Scholar]
  14. Nagelkerke J. F., Barto K. P., van Berkel T. J. In vivo and in vitro uptake and degradation of acetylated low density lipoprotein by rat liver endothelial, Kupffer, and parenchymal cells. J Biol Chem. 1983 Oct 25;258(20):12221–12227. [PubMed] [Google Scholar]
  15. Parthasarathy S., Steinbrecher U. P., Barnett J., Witztum J. L., Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 May;82(9):3000–3004. doi: 10.1073/pnas.82.9.3000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pitas R. E., Boyles J., Mahley R. W., Bissell D. M. Uptake of chemically modified low density lipoproteins in vivo is mediated by specific endothelial cells. J Cell Biol. 1985 Jan;100(1):103–117. doi: 10.1083/jcb.100.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Redgrave T. G., Roberts D. C., West C. E. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem. 1975 May 12;65(1-2):42–49. doi: 10.1016/0003-2697(75)90488-1. [DOI] [PubMed] [Google Scholar]
  18. Rohrer L., Freeman M., Kodama T., Penman M., Krieger M. Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature. 1990 Feb 8;343(6258):570–572. doi: 10.1038/343570a0. [DOI] [PubMed] [Google Scholar]
  19. Rosenfeld M. E., Khoo J. C., Miller E., Parthasarathy S., Palinski W., Witztum J. L. Macrophage-derived foam cells freshly isolated from rabbit atherosclerotic lesions degrade modified lipoproteins, promote oxidation of low-density lipoproteins, and contain oxidation-specific lipid-protein adducts. J Clin Invest. 1991 Jan;87(1):90–99. doi: 10.1172/JCI115006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  21. Van Berkel T. J., De Rijke Y. B., Kruijt J. K. Different fate in vivo of oxidatively modified low density lipoprotein and acetylated low density lipoprotein in rats. Recognition by various scavenger receptors on Kupffer and endothelial liver cells. J Biol Chem. 1991 Feb 5;266(4):2282–2289. [PubMed] [Google Scholar]
  22. Ylä-Herttuala S., Rosenfeld M. E., Parthasarathy S., Sigal E., Särkioja T., Witztum J. L., Steinberg D. Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. J Clin Invest. 1991 Apr;87(4):1146–1152. doi: 10.1172/JCI115111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. de Rijke Y. B., Jürgens G., Hessels E. M., Hermann A., van Berkel T. J. In vivo fate and scavenger receptor recognition of oxidized lipoprotein[a] isoforms in rats. J Lipid Res. 1992 Sep;33(9):1315–1325. [PubMed] [Google Scholar]
  24. de Rijke Y. B., van Berkel T. J. Rat liver Kupffer and endothelial cells express different binding proteins for modified low density lipoproteins. Kupffer cells express a 95-kDa membrane protein as a specific binding site for oxidized low density lipoproteins. J Biol Chem. 1994 Jan 14;269(2):824–827. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES