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. 1998 Aug 15;334(Pt 1):9–13. doi: 10.1042/bj3340009

Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor.

H Yoshida 1, N Kondratenko 1, S Green 1, D Steinberg 1, O Quehenberger 1
PMCID: PMC1219654  PMID: 9693095

Abstract

A new receptor for oxidized low-density lipoprotein (LDL), lectin-like oxidized LDL receptor-1 (LOX-1), has recently been cloned from bovine endothelial cells and human lung. A limited tissue-distribution study suggested that the protein was mainly produced by the vascular endothelium. In the present study we demonstrate that LOX-1 is also expressed in macrophages, where it may function as a scavenger receptor. LOX-1 was not detected in undifferentiated THP-1 cells or in freshly isolated human blood monocytes. However, mature human monocyte-derived macrophages and differentiated THP-1 cells showed high levels of LOX-1 transcripts. Consistent with these results, immunofluorescence staining and FACS analysis demonstrated that LOX-1 protein is expressed on the plasma membrane of macrophages. Western-blot analysis of membranes from macrophages (but not those from monocytes) identified a single band, with an apparent molecular mass of about 40 kDa, that displayed oxidized LDL-binding activity. These results suggest that differentiation induces the expression of LOX-1 in macrophages, where it may play a role as a scavenger receptor and/or a receptor for oxidized LDL.

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Selected References

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  1. Acton S. L., Scherer P. E., Lodish H. F., Krieger M. Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem. 1994 Aug 19;269(33):21003–21009. [PubMed] [Google Scholar]
  2. Berliner J. A., Navab M., Fogelman A. M., Frank J. S., Demer L. L., Edwards P. A., Watson A. D., Lusis A. J. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995 May 1;91(9):2488–2496. doi: 10.1161/01.cir.91.9.2488. [DOI] [PubMed] [Google Scholar]
  3. Brown M. S., Goldstein J. L. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. doi: 10.1146/annurev.bi.52.070183.001255. [DOI] [PubMed] [Google Scholar]
  4. Charo I. F., Myers S. J., Herman A., Franci C., Connolly A. J., Coughlin S. R. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2752–2756. doi: 10.1073/pnas.91.7.2752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Conti M., Morand P. C., Levillain P., Lemonnier A. Improved fluorometric determination of malonaldehyde. Clin Chem. 1991 Jul;37(7):1273–1275. [PubMed] [Google Scholar]
  7. 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]
  8. Geng Y., Kodama T., Hansson G. K. Differential expression of scavenger receptor isoforms during monocyte-macrophage differentiation and foam cell formation. Arterioscler Thromb. 1994 May;14(5):798–806. doi: 10.1161/01.atv.14.5.798. [DOI] [PubMed] [Google Scholar]
  9. Gerrity R. G. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981 May;103(2):181–190. [PMC free article] [PubMed] [Google Scholar]
  10. Giorda R., Rudert W. A., Vavassori C., Chambers W. H., Hiserodt J. C., Trucco M. NKR-P1, a signal transduction molecule on natural killer cells. Science. 1990 Sep 14;249(4974):1298–1300. doi: 10.1126/science.2399464. [DOI] [PubMed] [Google Scholar]
  11. 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]
  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. 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]
  14. 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]
  15. Lougheed M., Lum C. M., Ling W., Suzuki H., Kodama T., Steinbrecher U. High affinity saturable uptake of oxidized low density lipoprotein by macrophages from mice lacking the scavenger receptor class A type I/II. J Biol Chem. 1997 May 16;272(20):12938–12944. doi: 10.1074/jbc.272.20.12938. [DOI] [PubMed] [Google Scholar]
  16. Mackay C. R. Chemokine receptors and T cell chemotaxis. J Exp Med. 1996 Sep 1;184(3):799–802. doi: 10.1084/jem.184.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Murao K., Terpstra V., Green S. R., Kondratenko N., Steinberg D., Quehenberger O. Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes. J Biol Chem. 1997 Jul 11;272(28):17551–17557. doi: 10.1074/jbc.272.28.17551. [DOI] [PubMed] [Google Scholar]
  18. Nagase M., Hirose S., Fujita T. Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1). Biochem J. 1998 Mar 15;330(Pt 3):1417–1422. doi: 10.1042/bj3301417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nagase M., Hirose S., Sawamura T., Masaki T., Fujita T. Enhanced expression of endothelial oxidized low-density lipoprotein receptor (LOX-1) in hypertensive rats. Biochem Biophys Res Commun. 1997 Aug 28;237(3):496–498. doi: 10.1006/bbrc.1997.7176. [DOI] [PubMed] [Google Scholar]
  20. Nozaki S., Kashiwagi H., Yamashita S., Nakagawa T., Kostner B., Tomiyama Y., Nakata A., Ishigami M., Miyagawa J., Kameda-Takemura K. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects. J Clin Invest. 1995 Oct;96(4):1859–1865. doi: 10.1172/JCI118231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pearson A. M. Scavenger receptors in innate immunity. Curr Opin Immunol. 1996 Feb;8(1):20–28. doi: 10.1016/s0952-7915(96)80100-2. [DOI] [PubMed] [Google Scholar]
  22. Ramprasad M. P., Fischer W., Witztum J. L., Sambrano G. R., Quehenberger O., Steinberg D. The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9580–9584. doi: 10.1073/pnas.92.21.9580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ramprasad M. P., Terpstra V., Kondratenko N., Quehenberger O., Steinberg D. Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14833–14838. doi: 10.1073/pnas.93.25.14833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ryan J. C., Seaman W. E. Divergent functions of lectin-like receptors on NK cells. Immunol Rev. 1997 Feb;155:79–89. doi: 10.1111/j.1600-065x.1997.tb00941.x. [DOI] [PubMed] [Google Scholar]
  25. Sawamura T., Kume N., Aoyama T., Moriwaki H., Hoshikawa H., Aiba Y., Tanaka T., Miwa S., Katsura Y., Kita T. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997 Mar 6;386(6620):73–77. doi: 10.1038/386073a0. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Suzuki H., Kurihara Y., Takeya M., Kamada N., Kataoka M., Jishage K., Ueda O., Sakaguchi H., Higashi T., Suzuki T. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997 Mar 20;386(6622):292–296. doi: 10.1038/386292a0. [DOI] [PubMed] [Google Scholar]
  29. Tangirala R. K., Murao K., Quehenberger O. Regulation of expression of the human monocyte chemotactic protein-1 receptor (hCCR2) by cytokines. J Biol Chem. 1997 Mar 21;272(12):8050–8056. doi: 10.1074/jbc.272.12.8050. [DOI] [PubMed] [Google Scholar]
  30. Tokunaga K., Nakamura Y., Sakata K., Fujimori K., Ohkubo M., Sawada K., Sakiyama S. Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Cancer Res. 1987 Nov 1;47(21):5616–5619. [PubMed] [Google Scholar]
  31. Van Velzen A. G., Da Silva R. P., Gordon S., Van Berkel T. J. Characterization of a receptor for oxidized low-density lipoproteins on rat Kupffer cells: similarity to macrosialin. Biochem J. 1997 Mar 1;322(Pt 2):411–415. doi: 10.1042/bj3220411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yoshida H., Quehenberger O., Kondratenko N., Green S., Steinberg D. Minimally oxidized low-density lipoprotein increases expression of scavenger receptor A, CD36, and macrosialin in resident mouse peritoneal macrophages. Arterioscler Thromb Vasc Biol. 1998 May;18(5):794–802. doi: 10.1161/01.atv.18.5.794. [DOI] [PubMed] [Google Scholar]

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