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Lipoproteins modify the macrophage uptake of triacylglycerol emulsion and of zymosan particles by similar mechanisms

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Lipids

Abstract

The uptake of lipids and formation of foam cells are key events in atherosclerosis and in eruptive xanthomata formation in primary hyperchylomicronemia. Here we have compared the influence of low density lipoprotein (LDL), oxidized LDL (oxLDL), high density lipoprotein (HDL), and delipidated HDL (apoHDL) on the uptake by macrophages of zymosan (an insoluble fraction of yeast cell walls) and of triglyceride-rich emulsion (EM) particles that resemble chylomicrons, but, like zymosan, are equally devoid of protein components. Zymosan internalization is known to occur through unspecific phagocytosis, whereas natural chylomicrons are taken up by several specific lipoprotein receptors. We found that phagocytosis is not promoted as much by oxLDL as by normal LDL. HDL-coated zymosan was found to be inert and apoHDL slightly enhanced phagocytosis. LDL and apoHDL promoted the uptake of EM while oxLDL and HDL significantly inhibited the uptake. Therefore, the data support that HDL, and not apoHDL, particles inhibit EM uptake. We concluded that by using lipoprotein-coated zymosan particles, we could demonstrate different biological effects of LDL, oxLDL, HDL, and apoHDL on macrophage phagocytosis and that this method could be useful to delineate components of the various lipoproteins important for the propagation or inhibition of the formation of foam cells.

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Abbreviations

apoHDL:

delipidated high density lipoprotein

DMEM:

Dulbecco’s modified Eagle’s medium

EM:

chylomicron-like triglyceride-rich emulsions

FCS:

fetal calf serum

HDL:

high density lipoprotein

IgG:

immunoglobulin G

LDL:

low density lipoprotein

oxLDL:

oxidized LDL

PBS:

phosphate-buffered saline

TG:

triacylglycerol

VLDL:

very low density lipoprotein

[3H]-COE:

[1α,2α,(N)-3H]-cholesteryl oleoyl ether

References

  1. Ross, R. (1999) Atherosclerosis—An Inflammatory Disease, N. Engl. J. Med. 340, 115–126.

    Article  PubMed  CAS  Google Scholar 

  2. Khoo, J.C., Miller, E., Pio, F., Steinberg, D., and Witztum, J.L. (1992) Monoclonal Antibodies Against LDL Further Enhance Macrophage Uptake of LDL Aggregates, Arterioscler. Thromb. 12, 1258–1266.

    PubMed  CAS  Google Scholar 

  3. Goldstein, J.L., Ho, Y.K., Basu, S.K., and Brown, M.S. (1979) Binding Sites of Macrophages That Mediate Uptake and Degradation of Acetylated Low Density Lipoprotein, Producing Massive Cholesterol Deposition, Proc. Natl. Acad. Sci. USA 76, 333–337.

    Article  PubMed  CAS  Google Scholar 

  4. Dobrian, A., Lazar, V., Tirziu, D., and Simionescu, M. (1996) Increased Macrophage Uptake of Irreversibly Glycated Albumin Modified-Low Density Lipoprotein of Normal and Diabetic Subjects Is Mediated by Non-Saturable Mechanisms, Biochim. Biophys. Acta 1317, 5–14.

    PubMed  Google Scholar 

  5. Sparrow, C.P., Parthasarathy, S., and Steinberg, D. (1989) A Macrophage Receptor That Recognizes Oxidized Low Density Lipoprotein but Not Acetylated Low Density Lipoprotein, J. Biol. Chem. 264, 2599–2604.

    PubMed  CAS  Google Scholar 

  6. Karpe, F., Steiner, G., Uffelman, K., Olivecrona, T., and Hamsten, A. (1994) Postprandial Lipoproteins and Progression of Coronary Atherosclerosis, Atherosclerosis 106, 83–97.

    Article  PubMed  CAS  Google Scholar 

  7. Patsch, J.R., Miesenbock, G., Hopferwieser, T., Muhlberger, V., Knapp, E., Dunn, J.K., Gotto, A.M., Jr., and Patsch, W. (1992) Relation of Tryglyceride Metabolism and Coronary Artery Disease. Studies in Postprandial State, Arteroscler. Thomb. 12, 1336–1345.

    CAS  Google Scholar 

  8. Fisher, R.M., Humphries, S.E., and Talmud, P.J. (1997) Common Variation in the Lipoprotein Lipase Gene: Effects on Plasma Lipids and Risk of Atherosclerosis, Atherosclerosis 135, 145–159.

    Article  PubMed  CAS  Google Scholar 

  9. Yu, K.C.-W., Smith, D., Yamamoto, A., Kawguchi, A., Harada-Shiba, M., Yamamura, T., and Mamo, J.C.L. (1997) Phagocytic Degradation of Chylomicron Remnants by Fibroblasts from Subjects with Homozygous Familial Hypercholesterolaemia, Clin. Sci. 92, 197–203.

    PubMed  CAS  Google Scholar 

  10. Kruth, H.S., Skarlatos, S.I., Gaynor, P.M., and Gamble, W. (1994) Production of Cholesterol-Enriched Nascent High Density Lipoprotein by Human Monocyte-Derived Macrophages Is a Mechanism That Contributes to Macrophage Cholesterol Efflux, J. Biol. Chem. 269, 24511–24518.

    PubMed  CAS  Google Scholar 

  11. Atger, V., Giral, P., Simon, A., Cambillau, M., Leveson, J., Gariepy, J., Megnien, J.L., and Moatti, N. (1995) High-Density Subfractions as Markers of Early Atherosclerosis, Am. J. Cardiol. 75, 127–131.

    Article  PubMed  CAS  Google Scholar 

  12. Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C., and Witztum, J.L. (1989) Beyond Cholesterol. Modifications of Low Density Lipoprotein That Increase Its Atherogenicity, N. Engl. J. Med. 320, 915–924.

    Article  PubMed  CAS  Google Scholar 

  13. Schneider, W.J. (1997) Novel Members of the Low Density Lipoprotein Receptor Superfamily and Their Potential Roles in Lipid Metabolism, Curr. Opin. Lipidol. 8, 315–319.

    Article  PubMed  CAS  Google Scholar 

  14. Hoff, H.F., Whitaker, T.E., and O’Neil, J. (1992) Oxidation of Low Density Lipoprotein Leads to Particle Aggregation and Altered Macrophage Recogniton, J. Biol. Chem. 267, 602–609.

    PubMed  CAS  Google Scholar 

  15. Oliveira, H.C.F., Hirata, M.H., Redgrave, T.G., and Maranhão, R.C. (1998) Competition Between Chylomicrons and Their Remnants for Plasma Removal: a Study with Artificial Emulsion Models of Chylomicrons, Biochim. Biophys. Acta 958, 211–217.

    Google Scholar 

  16. Kesaniemi, Y.A., Witztum, J.L., and Steimbrecher, U.P. (1983) Receptor-Mediated Catabolism of Low Density Lipoprotein in Man. Quantitation Using Glycosylated Low Density Lipoprotein, J. Clin. Invest. 71, 950–959.

    PubMed  CAS  Google Scholar 

  17. Koizumi, J., Kano, M., Okabauashi, A.J., and Thompson, G.R. (1988) Behavior of Human Apolipoprotein A-I: Phospholipid ApoHDL: Phospholipid Complexes in Vitro and After Injection into Rabbits, J. Lipid Res. 29, 1405–1415.

    PubMed  CAS  Google Scholar 

  18. Heinecke, J.W., Rosen, H., and Chait, A. (1984) Iron and Copper Promote Modification of Low Density Lipoprotein by Human Arterial Smooth Muscle Cells in Culture, J. Clin. Invest. 74, 1890–1894.

    Article  PubMed  CAS  Google Scholar 

  19. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent, J. Biol. Chem. 193, 265–275.

    PubMed  CAS  Google Scholar 

  20. Miller, M.E. (1969) Phagocytosis in the Newborn Infant: Humoral and Cellular Factors, J. Pediatr. 74, 255–259.

    Article  PubMed  CAS  Google Scholar 

  21. Di Carlo, F.J., and Fiore, J.V. (1958) On the Composition of Zymosan, Science 127, 756–757.

    Article  Google Scholar 

  22. Zerbinatti, C.V., Oliveira, H.C.F., Wechster, S., and Quintão, E.C.R. (1991) Independent Regulation of Chylomicron Lipolysis and Particle Removal Rates: Effects of Insulin and Thyroid Hormones on the Metabolism of Artificial Chylomicrons, Metabolism 40, 1122–1127.

    Article  PubMed  CAS  Google Scholar 

  23. Benlian, P., Gennes, J.L., Foubert, L., Zhang, H., Gagné, S.E., and Hayden, M. (1996) Premature Atherosclerosis in Patients with Familial Chylomicronemia Caused by Mutations in the Lipoproteins Lipase Gene, N. Engl. J. Med. 335, 848–854.

    Article  PubMed  CAS  Google Scholar 

  24. Sung, S.J., Nelson, R.S., and Silverstein, S.C. (1983) Yeast Mannans Inhibit Binding and Phagocytosis of Zymosan by Mouse Peritoneal Macrophages, J. Cell. Biol. 96, 160–166.

    Article  PubMed  CAS  Google Scholar 

  25. Melamed, J., Medicus, R.G., Arnaout, M.A. and Colten, H.R. (1983) Induction of Granulocyte Histaminase Release by Particle Bound Complement C3 Cleavage Products (C3b, C3bi) and IgG, J. Immunol. 131, 439–444.

    PubMed  CAS  Google Scholar 

  26. Bigler, R.D., Khoo, M., Lund-Katz, S., Scerbo, L., and Esfahani, M. (1990) Identification of Low Density Lipoprotein as a Regulator of Fc Receptor-Mediated Phagocytosis, Proc. Nat. Acad. Sci. USA 87, 4981–4985.

    Article  PubMed  CAS  Google Scholar 

  27. Beppu, M., Hora, M., and Kikugawa, K. (1994) A Simple Method for the Assessment of Macrophage Scavenger Receptor-Ligand Interaction: Adherence of Erythrocytes Coated with Oxidized Low Density Lipoprotein and Modified Albumin to Macrophages, Biol. Pharm. Bull. 17, 39–46.

    PubMed  CAS  Google Scholar 

  28. Sambrano, G.R., Parthasarathy, S., and Steinberg, D. (1994) Recognition of Oxidatively Damaged Erythrocytes by a Macrophage Receptor with Specificity for Oxidized Low Density Lipoprotein, Proc. Natl. Acad. Sci. USA 91 3265–3269.

    Article  PubMed  CAS  Google Scholar 

  29. Gruarin, P., Stia, R., and Alessio, M. (1997) Formation of One or More Intrachain Disulphide Bonds Is Required for the Intracellular Processing and Transport of CD36, Biochem. J. 328, 635–642.

    PubMed  CAS  Google Scholar 

  30. Mamo, J.C.L., Elsegood, C.L., Gennat, H.C., and Yu, K.C.-W. (1996) Degradation of Chylomicron Remnants by Macrophages Occurs Via Phagocytosis, Biochemistry 35, 10210–10214.

    Article  PubMed  CAS  Google Scholar 

  31. Zhang, W.-Y., Gaynor, P.M., and Kruth, H.S. (1997) Aggregated Low Density Lipoprotein Induces and Enters Surface-Connected Compartments of Human Monocyte-Macrophages. Uptake Occurs Independently of the Low Density Lipoprotein Receptor, J. Biol. Chem. 272, 31700–31706.

    Article  PubMed  CAS  Google Scholar 

  32. Yu, K.C.-W., and Mamo, J.C.L. (1997) Regulation of Cholesterol Synthesis and Esterification in Primary Cultures of Macrophages Following Uptake of Chylomicron Remnants, Biochem. Mol. Biol. Int. 41, 33–39.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Schistosomiasis Immunopathology Laboratory (LIM/06), University of São Paulo Medical School, 01246-903, São Paulo, Brazil

    Célia M. V. Vendrame

  2. Lipids Laboratory (LIM/10), University of São Paulo Medical School, São Paulo, Brazil, Av. Dr. Arnaldo 455, s/3317, 01246-903, São Paulo, CEP, Brazil

    Márcia D. T. Carvalho, Vanessa E. Tobias, Alice F. Shimabukuro & Eder C. R. Quintão

  3. Department of Pathology, University of São Paulo Medical School, 01246-903, São Paulo, Brazil

    Magnus Gidlund

Authors
  1. Márcia D. T. Carvalho
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  2. Vanessa E. Tobias
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  3. Célia M. V. Vendrame
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  4. Alice F. Shimabukuro
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  5. Magnus Gidlund
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  6. Eder C. R. Quintão
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Correspondence to Eder C. R. Quintão.

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Carvalho, M.D.T., Tobias, V.E., Vendrame, C.M.V. et al. Lipoproteins modify the macrophage uptake of triacylglycerol emulsion and of zymosan particles by similar mechanisms. Lipids 35, 55–59 (2000). https://doi.org/10.1007/s11745-000-0494-1

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  • DOI: https://doi.org/10.1007/s11745-000-0494-1

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