Abstract
The characteristics of the recognition system involved in the receptor mediated endocytosis of the neoglycoprotein, fucose human serum albumin (HSA) were studied. It was found that (i) fucose-HSA showed strong affinity binding and uptake by various macrophages; (ii) binding was specific for L-fucose and D-mannose; (iii) binding was found to be inhibited by oxidant like H2O2 and swainsonine whereas it was elevated by dexamethasone; (iv) clearance of125I-fucose-HSA was rapid and strongly inhibited by unlabelled fucose-HSA. Greater than 70% of fucose-HSA was found in liver and more than 60% of this was found in liver lysosomes; (v) uptake of fucose-HSA was thirty-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (vi) moreover, mannose-HSA and ovalbumin which are potent inhibitors of mannose/N-acetylglucosamine receptors inhibited clearance and uptake of fucose-HSA by liver as well as by isolated Kupffer cells suggesting the involvement of both fucose and mannose receptors or a single type of receptor having greater affinity for fucose-HSA than for mannose-HSA. These results emphasize the important role of fucose-terminated glycoproteins in site-specific drug targeting.
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Neufeld EF, Ashwell G: Carbohydrate recognition systems for receptor-mediated pinocytosis. In: W.J. Lennarz (ed.). The Biochemistry of Glycoproteins and Proteoglycans. Plenum Press, New York, 1980, Ch. 6, pp 241–266
Stahl PD, Schlesinger PH: Receptor mediated pinocytosis of mannose/N-acetylglucosamine terminated glycoproteins and lysosomal enzymes by macrophages. Trends Biochem Sci 5: 194–196, 1980
Kaplan A, Achord DT, Sly WS: Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. Proc Natl Acad Sci USA 74: 2026–2030, 1977
Kawasaki T, Ashwell G: Chemical and physical properties of an hepatic membrane protein that specifically binds asialoglycoproteins. J Biol Chem 251: 1296–1302, 1976
Lehrman MA, Pizzo SV, Imber MJ, Hill RL: The binding of fucose-containing glycoproteins by hepatic lectins: Re-examination of the clearance from blood and the binding to membrane receptors and pure lectins. J Biol Chem 261: 7412–7418, 1986
Lehrman MA, Hill RL: The binding of fucose-containing glycoproteins by hepatic lectins: Purification of a fucose-binding lectin from rat liver. J Biol Chem 261: 7419–7425, 1986
Lehrman MA, Haltiwanger RS, Hill RL: The binding of fucosecontaining glycoproteins by hepatic lectins: The binding specificity of the rat liver fucose lectin. J Biol Chem 261: 7426–7432, 1986
Praaning-van Dalen DP, de Leeuw AM, Brouwer A, Knock DL: Rat liver endothelial cells have a greater capacity than Kupffer cells to endocytose N-acetylglucosamine and mannose-terminated glycoproteins. Hepatology 7: 672–679, 1987
Haltiwanger RS, Lehrman MA, Eckhardt AE, Hill RL: The distribution and localization of the fucose-binding lectin in rat tissues and the identification of a high affinity form of the mannose/N-acetylglucosamine-binding lectin in rat liver. J Biol Chem 261: 7433–7439, 1986
Chakraborty P, Bhaduri AN, Das PK: Sugar receptor mediated drug delivery to macrophages in the therapy of experimental visceral leishmaniasis. Biochem Biophys Res Commun 166: 404–410, 1990
Chakraborty P, Bhaduri AN, Das PK: Neoglycoproteins as carriers for receptor-mediated drug targeting in the treatment of experimental visceral leishmaniasis. J Protozool 37: 358–364, 1990
Sett R, Sarkar K, Das PK: Macrophage-directed delivery of doxorubicin conjugated to neoglycoprotein using leishmaniasis as the model disease. J Infec Dis 168: 994–999, 1993
Das PK, Murray GJ, Barranger JA: Studies on the turnover of glucocerebrosidase in cultured rat peritoneal macrophages and normal human fibroblasts. Eur J Biochem 154: 445–450, 1986
Brain JD, Frank R: Alveolar macrophage adhesion: Wash electrolyte composition and free cell yield. J Appl Physiol 34: 75–80, 1973
Lesser M, Chang JC, Galicki NI, Edelman J, Cardozo C: Cathepsin B and D activity in alveolar macrophages from rats with pulmonary granulomatous inflammation or acute lung injury. Agents Actions 28: 264–271, 1989
Lee SH, Crocker D, Gorden S: Macrophage plasma membrane and secretory properties in murine malaria. Effects of plasmodium yoelii. Bloodstage infection on macrophages in liver, spleen and blood. J Exp Med 163: 1862–1875, 1986
Berry MN, Friend DS: High yield preparation of isolated rat liver parenchymal cells. A biochemical and fine structural study. J Cell Biol 43: 506–520, 1969
Munthe-Kass AC, Seglen PO: The use of metrizamide as a gradient medium for isopycnic separation of rat liver cells. FEBS Lett 43: 252–256, 1974
Murray GJ: Lectin-specific targeting of lysosomal enzymes to reticuloendothelial cells. Methods Enzymol 149: 25–42, 1987
Dijkstra J, van Galen WJM, Hulstaert CE, Kalicharan D, Roerdink FH, Scherphof GL: Interaction of liposomes with Kupffer cells in vitro. Exp Cell Res 150: 161–176, 1984
Sayers TJ, Macher I, Chung J, Kugler E: The production of tumor necrosis factor by mouse bone marrow derived macrophages in response to bacterial lipopolysaccharide and a chemically synthesized monosaccharide precursor. J Immunol 138: 2935–2940, 1987
Chakraborty P, Das PK: Role of mannose/N-acetylglucosamine receptors in blood clearance and cellular attachment of Leishmania donovani. Mol Biochem Parasitol 28: 55–62, 1988
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with folin phenol reagent. J Biol Chem 193: 265–275, 1951
Dubois M, Gilles KA, Hamilton JK, Robers PA, Smith F: Colorimetric method for determination of sugars and related substances. Annal Chem 28: 350–356, 1956
Basu N, Sett R, Das PK: Down-regulation of mannose receptors on macrophages after infection with Leishmania donovani. Biochem J 277: 451–56, 1991
Gregoriadis G, Sourkes TL: Intracellular distribution of copper in the liver of the rat. Can J Biochem 45: 1841–1851, 1967
Stahl P, Schlesinger PH, Sigardson E, Rodman JS, Lee YC: Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: characterization and evidence for membrane recycling. Cell 19: 207–215, 1980
Shepherd VL, Abdolrasulnia R, Garett M, Cowan HB: Down-regulation of mannose receptor activity in macrophages after treatment with lipopolysaccharide and phorbol esters. J Immunol 145: 1530–1536, 1990
Bozeman PM, Hoidal JR, Shepherd VL: Oxidant-mediated inhibition of ligand uptake by the macrophage mannose receptor. J Biol Chem 263: 1240–1247, 1988
Shepherd VL, Konish MG, Stahl P: Dexamethasone increases expression of mannose receptors and decreases extracellular lysosomal enzyme accumulation in macrophages. J Biol Chem 260: 160–164, 1985
Ashwell G, Harford J: Carbohydrate specific receptors of the liver. Annu Rev Biochem 51: 531–554, 1982
Haltiwanger RS, Hill RL: The isolation of a rat alveolar macrophage lectin. J Biol Chem 261: 7440–7444, 1986
Haltiwanger RS, Hill RL: The ligand binding specificity and tissue localization of a rat alveolar macrophage lectin. J Biol Chem 261: 15696–15702, 1986
Stahl PD: The macrophage mannose receptor: current status. Am J Resp Cell Mol Biol 2: 317–318, 1990
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arkar, K., Sekhar Sarkar, H., Kole, L. et al. Receptor-mediated endocytosis of fucosylated neoglycoprotein by macrophages. Mol Cell Biochem 156, 109–116 (1996). https://doi.org/10.1007/BF00426332
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DOI: https://doi.org/10.1007/BF00426332