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. 1995 Feb 28;92(5):1391–1395. doi: 10.1073/pnas.92.5.1391

A macrophage receptor for oxidized low density lipoprotein distinct from the receptor for acetyl low density lipoprotein: partial purification and role in recognition of oxidatively damaged cells.

E Ottnad 1, S Parthasarathy 1, G R Sambrano 1, M P Ramprasad 1, O Quehenberger 1, N Kondratenko 1, S Green 1, D Steinberg 1
PMCID: PMC42525  PMID: 7533292

Abstract

The binding and uptake of oxidatively modified low density lipoprotein (OxLDL) by mouse peritoneal macrophages occurs, in part, via the well characterized acetyl LDL receptor. However, several lines of evidence indicate that as much as 30-70% of the uptake can occur via a distinct receptor that recognizes OxLDL with a higher affinity than it recognizes acetyl LDL. We describe the partial purification and characterization of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that specifically binds OxLDL. This receptor is shown to be distinct from the acetyl LDL receptor as well as from two other macrophage proteins that also bind OxLDL--the Fc gamma RII receptor and CD36. We suggest that this OxLDL-binding membrane protein participates in uptake of OxLDL by murine macrophages and also represents a receptor responsible for macrophage binding and phagocytosis of oxidatively damaged cells.

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Selected References

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

  1. Abrams J. M., Lux A., Steller H., Krieger M. Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10375–10379. doi: 10.1073/pnas.89.21.10375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arai H., Kita T., Yokode M., Narumiya S., Kawai C. Multiple receptors for modified low density lipoproteins in mouse peritoneal macrophages: different uptake mechanisms for acetylated and oxidized low density lipoproteins. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1375–1382. doi: 10.1016/0006-291x(89)92262-6. [DOI] [PubMed] [Google Scholar]
  3. Aronson N. N., Jr, Touster O. Isolation of rat liver plasma membrane fragments in isotonic sucrose. Methods Enzymol. 1974;31:90–102. doi: 10.1016/0076-6879(74)31009-9. [DOI] [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Duvall E., Wyllie A. H., Morris R. G. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology. 1985 Oct;56(2):351–358. [PMC free article] [PubMed] [Google Scholar]
  8. Endemann G., Stanton L. W., Madden K. S., Bryant C. M., White R. T., Protter A. A. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem. 1993 Jun 5;268(16):11811–11816. [PubMed] [Google Scholar]
  9. Fadok V. A., Voelker D. R., Campbell P. A., Cohen J. J., Bratton D. L., Henson P. M. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992 Apr 1;148(7):2207–2216. [PubMed] [Google Scholar]
  10. Fraser I., Hughes D., Gordon S. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature. 1993 Jul 22;364(6435):343–346. doi: 10.1038/364343a0. [DOI] [PubMed] [Google Scholar]
  11. Freeman M., Ekkel Y., Rohrer L., Penman M., Freedman N. J., Chisolm G. M., Krieger M. Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4931–4935. doi: 10.1073/pnas.88.11.4931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hara H., Tanishita H., Yokoyama S., Tajima S., Yamamoto A. Induction of acetylated low density lipoprotein receptor and suppression of low density lipoprotein receptor on the cells of human monocytic leukemia cell line (THP-1 cell). Biochem Biophys Res Commun. 1987 Jul 31;146(2):802–808. doi: 10.1016/0006-291x(87)90601-2. [DOI] [PubMed] [Google Scholar]
  14. Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis. 1983 Mar-Apr;3(2):149–159. doi: 10.1161/01.atv.3.2.149. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Krieger M., Acton S., Ashkenas J., Pearson A., Penman M., Resnick D. Molecular flypaper, host defense, and atherosclerosis. Structure, binding properties, and functions of macrophage scavenger receptors. J Biol Chem. 1993 Mar 5;268(7):4569–4572. [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Lee K. D., Pitas R. E., Papahadjopoulos D. Evidence that the scavenger receptor is not involved in the uptake of negatively charged liposomes by cells. Biochim Biophys Acta. 1992 Oct 19;1111(1):1–6. doi: 10.1016/0005-2736(92)90267-p. [DOI] [PubMed] [Google Scholar]
  19. McEvoy L., Williamson P., Schlegel R. A. Membrane phospholipid asymmetry as a determinant of erythrocyte recognition by macrophages. Proc Natl Acad Sci U S A. 1986 May;83(10):3311–3315. doi: 10.1073/pnas.83.10.3311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nishikawa K., Arai H., Inoue K. Scavenger receptor-mediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages. J Biol Chem. 1990 Mar 25;265(9):5226–5231. [PubMed] [Google Scholar]
  21. Oquendo P., Hundt E., Lawler J., Seed B. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989 Jul 14;58(1):95–101. doi: 10.1016/0092-8674(89)90406-6. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Salacinski P. R., McLean C., Sykes J. E., Clement-Jones V. V., Lowry P. J. Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent, 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl glycoluril (Iodogen). Anal Biochem. 1981 Oct;117(1):136–146. doi: 10.1016/0003-2697(81)90703-x. [DOI] [PubMed] [Google Scholar]
  24. Sambrano G. R., Parthasarathy S., Steinberg D. Recognition of oxidatively damaged erythrocytes by a macrophage receptor with specificity for oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3265–3269. doi: 10.1073/pnas.91.8.3265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Savill J., Dransfield I., Hogg N., Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 1990 Jan 11;343(6254):170–173. doi: 10.1038/343170a0. [DOI] [PubMed] [Google Scholar]
  26. Savill J., Fadok V., Henson P., Haslett C. Phagocyte recognition of cells undergoing apoptosis. Immunol Today. 1993 Mar;14(3):131–136. doi: 10.1016/0167-5699(93)90215-7. [DOI] [PubMed] [Google Scholar]
  27. Schwartz C. J., Ghidoni J. J., Kelley J. L., Sprague E. A., Valente A. J., Suenram C. A. Evolution of foam cells in subcutaneous rabbit carrageenan granulomas: I. Light-microscopic and ultrastructural study. Am J Pathol. 1985 Jan;118(1):134–150. [PMC free article] [PubMed] [Google Scholar]
  28. Sparrow C. P., Parthasarathy S., Steinberg D. A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. J Biol Chem. 1989 Feb 15;264(5):2599–2604. [PubMed] [Google Scholar]
  29. Stanton L. W., White R. T., Bryant C. M., Protter A. A., Endemann G. A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein. J Biol Chem. 1992 Nov 5;267(31):22446–22451. [PubMed] [Google Scholar]
  30. Steinberg D. Arterial metabolism of lipoproteins in relation to atherogenesis. Ann N Y Acad Sci. 1990;598:125–135. doi: 10.1111/j.1749-6632.1990.tb42284.x. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Via D. P., Pons L., Dennison D. K., Fanslow A. E., Bernini F. Induction of acetyl-LDL receptor activity by phorbol ester in human monocyte cell line THP-1. J Lipid Res. 1989 Oct;30(10):1515–1524. [PubMed] [Google Scholar]
  34. 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]

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