Skip to main content
Log in

Interaction of lipid transfer protein with plasma lipoproteins and cell membranes

  • Published:
Experientia Aims and scope Submit manuscript

Summary

The hydrophobic lipid components of lipoproteins, cholesteryl ester and triglyceride, are transferred between all lipoproteins by a specific plasma glycoprotein, termed lipid transfer protein (LTP). LTP facilitates lipid transfer by an exchange process in which cholesteryl ester and triglyceride compete for transfer. Thus, LTP promotes remodeling of the lipoprotein structure, and plays an important role in the intravascular metabolism of these particles and in the lipoprotein-dependent pathways of cholesterol clearance from cells. The properties of LTP, its mechanisms of action, its roles in lipoprotein metabolism, and its modes of regulation are reviewed along with recent data that suggest a possible role for this protein in directly modifying cellular lipid composition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literatur

  1. Abbey, M., Bastiras, S., and Calvert, G. D., Immunoprecipition of lipid transfer protein activity by an antibody against human plasma lipid transfer protein-I. Biochim. biophys. Acta833 (1985) 25–33.

    Article  CAS  PubMed  Google Scholar 

  2. Abbey, M., and Calvert, G. D., Effects of blocking plasma lipid transfer protein activity in the rabbit. Biochim. biophys. Acta1003 (1989) 20–29.

    Article  CAS  PubMed  Google Scholar 

  3. Akanuma, Y., and Glomset, J., In vitro incorporation of cholesterol-14C into very low density lipoprotein cholesteryl esters. J. Lipid Res.9 (1968) 620–626.

    Article  CAS  PubMed  Google Scholar 

  4. Albers, J. J., Tollefson, J. H., Chen, C.-H., and Steinmetz, A., Isolation and characterization of human lipid transfer proteins. Arteriosclerosis4 (1984) 49–58.

    Article  CAS  PubMed  Google Scholar 

  5. Albers, J. J., Tollefson, J. H., Faust, R. A., and Nishide, T., Plasma cholesteryl ester and phospholipid transfer proteins and their regulation. Adv. exp. Med. Biol.243 (1988) 213–217.

    Article  CAS  PubMed  Google Scholar 

  6. Bagdade, J. D., Ritter, M., Levy, R., and Subbaiah, P. V., Accelerated cholesterol ester transfer and abnormal surface lipoprotein composition in type 1 diabetics. Circulation76, Suppl. IV (1987) 416.

    Google Scholar 

  7. Barter, P. J., Gooden, J. M., and Rajaram, O. V., Species differences in the activity of a serum triglyceride transferring factor. Atherosclerosis33 (1979) 165–169.

    Article  CAS  PubMed  Google Scholar 

  8. Barter, P. J., Hopkins, G. J., Gorjatschko, L., and Jones, M., Competitive inhibition of plasma cholesterol esterification by human highdensity lipoprotein-subfraction 2. Biochim. biophys. Acta793 (1984) 260–268.

    Article  CAS  PubMed  Google Scholar 

  9. Barter, P. J., Hopkins, G. J., and Calvert, G. D., Transfers and exchanges of esterified cholesterol between plasma lipoproteins. Biochem. J.208 (1982) 1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Barter, P. J., Hopkins, G. J., Gorjatschko, L., and Jones, M. E., A unified model of esterified cholesterol exchanges between human plasma lipoproteins. Atherosclerosis44 (1982) 27–40.

    Article  CAS  PubMed  Google Scholar 

  11. Barter, P. J., and Lally, J. I., In vitro exchange of esterified cholesterol between serum lipoprotein fractions: Studies of humans and rabbits. Metabolism28 (1979) 230–236.

    Article  CAS  PubMed  Google Scholar 

  12. Barter, P. J., Lally, J. I., and Wattchow, D., Metabolism of triglyceride in rabbit plasma low and high density lipoproteins: Studies in vivo and in vitro. Metabolism28 (1979) 614–618.

    Article  CAS  PubMed  Google Scholar 

  13. Deckelbaum, R. J., Eisenberg, S., Oschry, Y., Granot, E., Sharon, I., and Bengtsson-Olivecrona, G., Conversion of human plasma high density lipoprotein-2 to high density lipoprotein-3: Roles of neutral lipid exchange and triglyceride lipases. J. biol. Chem.261 (1986) 5201–5208.

    Article  CAS  PubMed  Google Scholar 

  14. Deckelbaum, R. J., Eisenberg, S., Fainaru, M., Barenholz, Y., and Olivecrona, T., In vitro production of human plasma low density lipoprotein-like particles: A model for very low density lipoprotein catabolism. J. biol. Chem.254 (1979) 6079–6087.

    Article  CAS  PubMed  Google Scholar 

  15. Deckelbaum, R. J., Eisenberg, S., Oschry, Y., and Rudel, L. L., Neutral lipid transfer and lipolysis convert high molecular weight LDL from cholesterol-fed nonhuman primates towards normal: a molecular analysis. Biochim. biophys. Acta961 (1988) 223–233.

    Article  CAS  PubMed  Google Scholar 

  16. Deckelbaum, R. J., Eisenberg, S., Oschry, Y., Butbul, E., Sharon, I., and Olivecrona, T., Reversible modification of human plasma low density lipoproteins toward triglyceride-rich particles: A mechanism for losing excess cholesterol esters. J. biol. Chem.257 (1982) 6509–6517.

    Article  CAS  PubMed  Google Scholar 

  17. Dieplinger, H., Schoenfeld, P. Y., and Fielding, C. J., Plasma cholesterol metabolism in end-stage renal disease: Differences between treatment by hemodialysis or peritoneal dialysis. J. clin. Invest.77 (1986) 1071–1083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Drayna, D., Jarnagin, A. S., McLean, J., Henzel, W., Kohr, W., Fielding, C., and Lawn R., Cloning and sequencing of human cholesteryl ester transfer protein cDNA. Nature327 (1987) 632–634.

    Article  CAS  PubMed  Google Scholar 

  19. Ellsworth, J. L., Kraemer, F. B., and Cooper, A. D., Transport of β-very low density lipoproteins and chylomicron remnants by macrophages is mediated by the low density lipoprotein receptor pathway. J. biol. Chem.262 (1987) 2316–2325.

    Article  CAS  PubMed  Google Scholar 

  20. Faust, R. A., and Albers, J. J., Regulated vectorial secretion of cholesteryl ester transfer protein (LTP-1) by the CaCo-2 model of human enterocyte epithelium. J. biol. Chem.263 (1988) 8786–8789.

    Article  CAS  PubMed  Google Scholar 

  21. Fielding, C. J., and Fielding, P. E., Regulation of human plasma lecithin:cholesterol acyltransferase activity by lipoprotein acceptor cholesteryl ester content. J. biol. Chem.256 (1981) 2102–2104.

    Article  CAS  PubMed  Google Scholar 

  22. Fielding, C. J., Reaven, G. M., Liu, G., and Fielding, P. E., Increased free cholesterol in plasma low and very low density lipoproteins in non-insulin-dependent diabetes mellitus: Its role in the inhibition of cholesteryl ester transfer. Proc. natl Acad. Sci. USA81 (1984) 2512–2516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fielding, C. J., The origin and properties of free cholesterol potential gradients in plasma, and their relation to atherogenesis. J. Lipid Res.25 (1984) 1624–1628.

    Article  CAS  PubMed  Google Scholar 

  24. Fielding, P. E., Fielding, C. J., Havel, R. J., Kane, J. P., and Tun, P., Cholesterol net transport, esterification, and transfer in human hyperlipidemic plasma. J. clin. Invest.71 (1983) 449–460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Glomset, J. A., The plasma lecithin: cholesterol acyltransferase reaction. J. Lipid Res.9 (1968) 155–167.

    Article  CAS  PubMed  Google Scholar 

  26. Granot, E., Tabas, I., and Tall, A. R., Human plasma cholesteryl ester transfer protein enhances the transfer of cholesteryl ester from high density lipoproteins into cultured HepG2 cells. J. biol. Chem.262 (1987) 3482–3487.

    Article  CAS  PubMed  Google Scholar 

  27. Groener, J. E. M., Van Gent, T., and Van Tol, A., Effect of lipid transfer protein on plasma lipids, apolipoproteins and metabolism of high-density lipoprotein cholesteryl ester in the rat. Biochim. biophys. Acta1002 (1989) 93–100.

    Article  CAS  PubMed  Google Scholar 

  28. Ha, Y. C., Chang, L. B. F., and Barter, P. J., Effects of injecting exogenous lipid transfer protein into rats. Biochim. biophys. Acta833 (1985) 203–210.

    Article  CAS  PubMed  Google Scholar 

  29. Hashimoto, S., Morton, R. E., and Zilversmit, D. B., Facilitated transfer of cholesteryl ester between rough and smooth microsomal membranes by plasma lipid transfer protein. Biochem. biophys. Res. Commun.120 (1984) 586–592.

    Article  CAS  PubMed  Google Scholar 

  30. Hesler, C. B., Swenson, T. L., and Tall, A. R., Purification and characterization of a human plasma cholesteryl ester transfer protein. J. biol. Chem.262 (1987) 2275–2282.

    Article  CAS  PubMed  Google Scholar 

  31. Hesler, C. B., Tall, A. R., Swenson, T. L., Weech, P. K., Marcel, Y. L., and Milne, R. W., Monoclonal antibodies to the Mr 74,000 cholesteryl ester transfer protein neutralize all of the cholesteryl ester and triglyceride transfer activities in human plasma. J. biol. Chem.263 (1988) 5020–5023

    Article  CAS  PubMed  Google Scholar 

  32. Hopkins, G. J., and Barter, P. J., Capacity of lipoproteins to act as substrates for lecithin-cholesterol acyltransferase: Enhancement by pre-incubation with an artificial triacylglycerol emulsion. Biochim. biophys. Acta794 (1984) 31–40.

    Article  CAS  PubMed  Google Scholar 

  33. Hopkins, G. J., and Barter, P. J., Role of esterified cholesterol transfers in the regulation of plasma cholesterol esterification. Atherosclerosis49 (1983) 177–185.

    Article  CAS  PubMed  Google Scholar 

  34. Thm, J., Ellsworth, J. L., Chataing, B., and Harmony, J. A. K., Plasma protein-facilitated coupled exchange of phosphatidylcholine and cholesteryl ester in the absence of cholesterol esterification. J. biol. Chem.257 (1982) 4818–4827.

    Article  Google Scholar 

  35. Ihm, J., Harmony, J. A. K., Ellsworth, J., and Jackson, R. L., Simultaneous transfer of cholesteryl ester and phospholipid by protein(s) isolated from human lipoprotein-free plasma. Biochem. biophys. Res. Commun.93 (1980) 1114–1120.

    Article  CAS  PubMed  Google Scholar 

  36. Ihm, J., Quinn, D. M., Busch, S. J., Chataing, B., and Harmony, J. A. K., Kinetics of plasma protein-catalyzed exchange of phosphatidylcholine and cholesteryl ester between plasma lipoproteins. J. Lipid Res.23 (1982) 1328–1341.

    Article  CAS  PubMed  Google Scholar 

  37. Jarnagin, A. S., Kohr, W., and Fielding, C., Isolation and specificity of a Mr 74,000 cholesteryl ester transfer protein from human plasma. Proc. natl Acad. Sci. USA84 (1987) 1854–1857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Koizumi, J., Mabuchi, H., Yoshimura, A., Michishita, I., Takeda, M., Itoh, H., Sakai, Y., Sakai, T., Ueda, K., and Takeda, R., Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. Atherosclerosis58 (1985) 175–186.

    Article  CAS  PubMed  Google Scholar 

  39. Kuksis, A., Myher, J. J., Geher, K., Jones, G. J. L., Breckenridge, W. C., Feather, T., Hewitt, D., and Little, J. A., Decreased plasma phosphatidylcholine/free cholesterol ratio as indicator of risk for ischemic vascular disease. Arteriosclerosis2 (1982) 296–302.

    Article  CAS  PubMed  Google Scholar 

  40. Loudet, A.-M., Dousset, N., Perret, B., Ierides, M., Carton, M., and Douste-Blazy, L., Triacylglycerol increase in plasma very low density lipoproteins in cyclophosphamide-treated rabbit: relationship with cholesteryl ester transfer activity. Biochim. biophys. Acta836 (1985) 376–384.

    Article  CAS  PubMed  Google Scholar 

  41. Mills, G. L., and Taylaur, C. E., The distribution and composition of serum lipoproteins in eighteen animals. Comp. Biochem. Physiol.40B (1971) 489–501.

    CAS  Google Scholar 

  42. Morton, R. E., Binding of plasma-derived lipid transfer protein to lipoprotein substrates. J. biol. Chem.260 (1985) 12593–12599.

    Article  CAS  PubMed  Google Scholar 

  43. Morton, R. E., Free cholesterol is a potent regulator of lipid transfer protein function. J. biol. Chem.263 (1988) 12 235–12 241.

    Article  CAS  Google Scholar 

  44. Morton, R. E., Interaction of plasma-derived lipid transfer protein with macrophages in culture. J. Lipid Res.29 (1988) 1367–1377.

    Article  CAS  PubMed  Google Scholar 

  45. Morton, R. E., Specificity of lipid transfer protein for molecular species of cholesteryl ester. J. Lipid Res.27 (1986) 523–529.

    Article  CAS  PubMed  Google Scholar 

  46. Morton, R. E., and Zilversmit, D. B., Inter-relationship of lipids transferred by the lipid-transfer protein isolated from human lipoprotein-deficient plasma. J. biol. Chem.258 (1983) 11 751–11 757.

    Article  CAS  Google Scholar 

  47. Morton, R. E., and Zilversmit, D. B., A plasma inhibitor of triglyceride and cholesteryl ester transfer activities. J. biol. Chem.256 (1981) 11 992–11 995.

    Article  CAS  Google Scholar 

  48. Morton, R. E., and Zilversmit, D. B., Purification and characterization of lipid transfer protein(s) from human lipoprotein-deficient plasma. J. Lipid Res.23 (1982) 1058–1067.

    Article  CAS  PubMed  Google Scholar 

  49. Muzya, G. I., Korobkova, E. N., Golovanova, N. K., and Bergelson, L. D., Influence of prostaglandins on the lipid transfer between human high density and low density lipoproteins. FEBS Lett.220 (1987) 371–375.

    Article  CAS  PubMed  Google Scholar 

  50. Nagashima, M., McLean, J. W., and Lawn, R. M., Cloning and mRNA tissue distribution of rabbit cholesteryl ester transfer protein. J. Lipid Res.29 (1988) 1643–1649.

    Article  CAS  PubMed  Google Scholar 

  51. Nichols, A. V., and Smith, L., Effect of very low-density lipoproteins on lipid transfer in incubated serum. J. Lipid Res.6 (1965) 206–210.

    Article  CAS  PubMed  Google Scholar 

  52. Nishide, T., Tollefson, J. H., and Albers, J. J., Inhibition of lipid transfer by a unique high density lipoprotein subclass containing an inhibitor protein. J. Lipid Res.30 (1989) 149–158.

    Article  CAS  PubMed  Google Scholar 

  53. Nishikawa, O., Yokoyama, S., Okabe, H., and Yamamoto, A., Enhancement of non-polar lipid transfer reaction through stabilization of substrate lipid particles with apolipoproteins. J. Biochem.103 (1988) 188–194.

    Article  CAS  PubMed  Google Scholar 

  54. Oschry, Y., and Eisenberg, S., Rat plasma lipoproteins: re-evaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity. J. Lipid Res.23 (1982) 1099–1106.

    Article  CAS  PubMed  Google Scholar 

  55. Pattnaik, N. M., Montes, A., Hughes, L. B., and Zilversmit, D. B., Cholesteryl ester exchange protein in human plasma: Isolation and characterization. Biochim. biophys. Acta530 (1978) 428–438.

    Article  CAS  PubMed  Google Scholar 

  56. Pattnaik, N. M., and Zilversmit, D. B., Interaction of cholesteryl ester exchange protein with human plasma lipoproteins and phospholipid vesicles. J. biol. Chem.254 (1979) 2782–2786.

    Article  CAS  PubMed  Google Scholar 

  57. Philipps, M. C., Johnson, W. J., and Rothblat, G. H., Mechanisms and consequences of cellular cholesterol exchange and transfer. Biochim. biophys. Acta906 (1987) 223–276.

    Article  Google Scholar 

  58. Quig, D. W., and Zilversmit, D. B., Plasma lipid transfer acitivty in rabbits: effects of dietary hyperlipidemias. Atherosclerosis70 (1988) 263–271.

    Article  CAS  PubMed  Google Scholar 

  59. Rajaram, O. V., White, G. H., and Barter, P. J., Partial purification and characterization of a triacylglycerol-transfer protein from rabbit serum. Biochim. biophys. Acta617 (1980) 383–392.

    Article  CAS  PubMed  Google Scholar 

  60. Rinninger, F., and Pittman, R. C., Mechanism of the cholesteryl ester transfer protein-mediated uptake of high density lipoprotein cholesteryl esters by Hep G2 cells. J. biol. Chem.264 (1989) 6111–6118.

    Article  CAS  PubMed  Google Scholar 

  61. Sammett, D., and Tall, A. R., Mechanisms of enhancement of cholesteryl ester transfer protein activity by lipolysis. J. biol. Chem.260 (1985) 6687–6697.

    Article  CAS  PubMed  Google Scholar 

  62. Schneider, H., Morrod, R. S., Colvin, J. R., and Tattrie, N. H., The lipid core model of lipoproteins. Chem. Phys. Lipids10 (1973) 328–353.

    Article  CAS  PubMed  Google Scholar 

  63. Segrest, J.P., and Jackson, R. L., Molecular weight determination of glycoproteins by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Meth. Enzymol.28 (1972) 54–63.

    Article  Google Scholar 

  64. Shen, B. W., Scanu, A. M., and Kézdy, F. J., Structure of human serum lipoproteins inferred from compositional analysis. Proc. natl Acad. Sci. USA74 (1977) 837–841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Son, Y.-S. C., and Zilversmit, D. B., Increased lipid transfer activities in hyperlipidemic rabbit plasma. Arteriosclerosis6 (1986) 345–351.

    Article  CAS  PubMed  Google Scholar 

  66. Son, Y.-S. C., and Zilversmit, D. B., Purification and characterization of human plasma proteins that inhibit transfer activities. Biochim. biophys. Acta795 (1984) 473–480.

    Article  CAS  PubMed  Google Scholar 

  67. Stein, O., Halperin, G., and Stein, Y., Cholesteryl ester efflux from extracellular and cellular elements of the arterial wall. Arteriosclerosis6 (1986) 70–78.

    Article  CAS  PubMed  Google Scholar 

  68. Stein, Y., Stein, O., Olivecrona, T., and Halperin, G., Putative role of cholesteryl ester transfer protein in removal of cholesteryl ester from vascular interstitium, studied in a model system in cell culture. Biochim. biophys. Acta834 (1985) 336–345.

    Article  CAS  PubMed  Google Scholar 

  69. Swenson, T. L., Brocia, R. W., and Tall, A. R., Plasma cholesteryl ester transfer protein has binding sites for neutral lipids and phospholipids. J. biol. Chem.263 (1988) 5150–5157.

    Article  CAS  PubMed  Google Scholar 

  70. Swenson, T. L., Simmons, J. S., Hesler, C. B., Bisgaier, C., and Tall, A. R., Cholesteryl ester transfer protein is secreted by Hep G2 cells and contains asparagine-linked carbohydrate and sialic acid. J. biol. Chem.262 (1987) 16 271–16 274.

    Article  CAS  Google Scholar 

  71. Tall, A. R., Abreu, E., and Shuman, J., Separation of a plasma phospholipid transfer protein from cholesterol ester/phospholipid exchange protein. J. biol. Chem.258 (1983) 2174–2180.

    Article  CAS  PubMed  Google Scholar 

  72. Tall, A. R., Sammett, D., Vita, G. M., Deckelbaum, R., and Olivecrona, T., Lipoprotein lipase enhances the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from high density lipoproteins to very low density lipoproteins. J. biol. Chem.259 (1984) 9587–9594.

    Article  CAS  PubMed  Google Scholar 

  73. Tall, A., Sammett, D., and Granot, E., Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia. J. clin. Invest.77 (1986) 1163–1172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Tollefson, J. H., Faust, R., Albers, J. J., and Chait, A., Secretion of a lipid transfer protein by human monocyte-derived macrophages. J. biol. Chem.260 (1985) 5887–5890.

    Article  CAS  PubMed  Google Scholar 

  75. Tollefson, J. H., Liu, A., and Albers, J. J., Regulation of plasma lipid transfer by the high-density lipoproteins. Am. J. Physiol.255 (1988) E894-E902.

    CAS  PubMed  Google Scholar 

  76. Tollefson, J. H., Ravnik, S., and Albers, J. J., Isolation and characterization of a phospholipid transfer protein (LTP-II) from human plasma. J. Lipid Res.29 (1988) 1593–1602.

    Article  CAS  PubMed  Google Scholar 

  77. Weinberg, R. B., and Scanu, A. M., In vitro reciprocal exchange of apoproteins and nonpolar lipids between human high density lipoproteins and an artificial triglyceride-phospholipid emulsion (Intralipid). Atherosclerosis44 (1982) 141–152.

    Article  CAS  PubMed  Google Scholar 

  78. Whitlock, M. E., Swenson, T. L., Ramakrishnan, R., Leonard, M. T., Marcel, Y. L., Milne, R. W., and Tall, A. R., Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism. J. clin. Invest.84 (1989) 129–137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yamashita, S., Matsuzawa, Y., Okazaki, M., Kako, H., Yasugi, T., Akioka, H., Hirano, K., and Tarui, S., Small polydisperse low density lipoproteins in familial hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity. Atherosclerosis70 (1988) 7–12.

    Article  CAS  PubMed  Google Scholar 

  80. Zilversmit, D. B., Hughes, L. B. and Balmer, J., Stimulation of cholesterol ester exchange by lipoprotein-free rabbit plasma. Biochim. biophys. Acta409 (1975) 393–398.

    Article  CAS  PubMed  Google Scholar 

  81. Zilversmit, D. B., Morton, R. E., Hughes, L. B., and Thompson, K. H., Exchange of retinyl and cholesteryl esters between lipoproteins of rabbit plasma. Biochim. biophys. Acta712 (1982) 88–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morton, R.E. Interaction of lipid transfer protein with plasma lipoproteins and cell membranes. Experientia 46, 552–560 (1990). https://doi.org/10.1007/BF01939693

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01939693

Key words

Navigation