Abstract
The present study was prompted by findings in our laboratory showing that serum effectively inhibits scavenger receptor (SR)-mediated endocytosis in hepatic sinusoidal endothelial cells (SEC). Experiments with SEC in vitro showed that the presence of 20% human serum inhibited endocytosis of SR ligands, 125I-formaldehyde treated bovine serum albumin (FSA) and 125I-nidogen, by 30 and 50%, respectively, whereas pre-heated foetal bovine serum (10%) inhibited endocytosis of 125I-FSA by as much as 56%. Human, bovine and rat serum had similar inhibitory effect on endocytosis in SEC. Fractionation of foetal bovine and human serum on anion exchange chromatography demonstrated that the inhibitory principle co-purified with macromolecules of high negative charge. The serum fraction that most effectively inhibited SR-mediated endocytosis of 125I-FSA did not affect mannose receptor-mediated endocytosis of 125I-mannan to the same extent. Trap-labelled negatively charged serum fraction administered intravenously to rats was eliminated almost exclusively by liver, with a blood decay of 50% over the first 3 min after injection. Isolation of liver cells showed that the populations of Kupffer cells and SEC contained 39 and 61% of liver radioactivity 30 min after injection of trap-labelled negatively charged fractions prepared from pre-heated (‘complement inactivated’) foetal bovine sera. These findings suggest that the process of serum formation from native blood generates appreciable amounts of macromolecules that compete specifically with the SR for endocytosis in SEC. The inhibitory power of pre-heated serum is particularly great. For this reason pre-heated serum should be used with caution in studies of SR in SEC.
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Smedsrød B, Seternes T, Sørensen K, Lindhe Ö, Sveinbjörnsson B: Scavenger endothelial cells. Cells Hepat Sinus 7: 147–152, 1999
Smedsrød B, Melkko J, Risteli L, Risteli J: Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells. Biochem J 271: 345–350, 1990
Smedsrød B, Einarsson M: Clearance of tissue plasminogen activator by mannose and galactose receptors in the liver. Thromb Haemostasis 63: 60–66, 1990
Smedsrød B, Eriksson S, Fraser JRE, Laurent TC, Pertoft H: Properties of liver endothelial cells in primary monolayer cultures. In: DL Knook, E Wisse (eds). Sinusoidal Liver Cells. Elsevier Biomedical Press, Amsterdam, 1982, pp 263–270
Smedsrød B, Tollersrud OK: Sinusoidal liver endothelial cells recruit lysosomal enzymes from the circulation by mannose-receptor mediated endocytosis. Cells Hepat Sinus 5: 180–183, 1995
Brown MS, Goldstein JL: Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52: 223–261, 1983
Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudair P, Krieger M: Type I macrophage scavenger receptor contains α-helical and collagen-like coiled coils. Nature 343: 531–535, 1990
Rohrer L, Freeman M, Kodama T, Penman M, Krieger M: Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature 343: 570–572, 1990
Endemann G, Stanton LW, Madden KS, Bryant CM, White T, Protte AA: CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 268: 11811–11816, 1993
Acton SL, Scherer PE, Lodish HF, Krieger M: Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem 269: 21003–21009, 1994
Fukasawa M, Hirota K, Adachi H, Mimura K, Murakami-Murofushi K, Tsujimoto M, Arai H, Inoue K: Chinese hamster ovary cells expressing a novel type of acetylated low density lipoprotein receptor. J Biol Chem 270: 1921–1927, 1995
Nazarova VL, Andreeva ER, Tertov VV, Gel'dieva BS, Orekhov AN: Immuncytochemical study of the localization of scavenger receptor in human aortic smooth-muscle cells. Bull Exp Biol Med 120: 839–842, 1995
Pitas RE: Expression of the acetyl low density lipoprotein receptor by rabbit fibroblasts and smooth muscle cells. J Biol Chem 265: 12722–12727, 1990
Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T: An endothelial receptor for oxidized low-density lipoprotein. Nature 386: 73–77, 1997
Lucarelli M, Gennarelli M, Cardelli P, Novell G, Scarpa S, Dallapiccola B, Strom R: Expression of receptors for native and chemically modified low-density lipoproteins in brain microvessels. FEBS Lett 401: 53–58, 1997
Geng Y-J, Hansson GK: High endothelial cells of postcapillary venules express the scavenger receptor in human peripheral lymph nodes. Scand J Immunol 42: 289–296, 1995
Mizutani T, Sonoda Y, Minegishi T, Wakabayashi K, Miyamoto K: Cloning, characerization, and cellular distribution of rat scavenger receptor class B type I (SR-BI) in the ovary. Biochem Biophys Res Commun 234: 499–505, 1997
Webb NR, de Villiers WJS, Connell PM, de Beer FC, van der Westhuyzen DR: Alternative forms of the scavenger receptor BI (SR-BI). J Lipid Res 38: 1490–1495, 1997
Brunskill NJ, Nahorski S, Walls J: Characteristics of albumin binding to opossum kidney cells and identification of potential receptors. Pflügers Arch Eur J Physiol 433: 497–504, 1997
Holmskov U, Lawson P, Teisner B, Tornøe I, Willis AC, Morgan C, Koch C, Reid KBM: Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule. J Biol Chem 272: 13743–13749, 1997
Krieger M: The other side of scavenger receptors: Pattern recognition for host defence. Curr Opin Lipidol 8: 275–280, 1997
Terpstra V, van Amersfoort ES, van Velzen AG, Kuiper J, van Berkel TJC: Hepatic and extrahepatic scavenger receptors: Function in relation to disease. Arterioscler Thromb Vasc Biol 20: 1860–1872, 2000
Greaves DR, Gough PJ, Gordon S: Recent progress in defining the role of scavenger receptors in lipid transport, atherosclerosis and host defence. Curr Opin Lipidol 9: 425–432, 1998
Fraser I, Hughes D, Gordon S: Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature 364: 343–346, 1993
Hughes DA, Fraser IP, Gordon S: Murine MØ scavenger receptor: Adhesion function and expression. Immunol Lett 43: 7–14, 1994
Yokota T, Ehlin-Henriksson B, Hansson GK: Scavenger receptors mediate adhesion of activated B lymphocytes. Exp Cell Res 239: 16–22, 1998
Zingg JM, Ricciarelli R, Azzi A: Scavenger receptors and modified lipoproteins: Fatal attractions? IUBMB Life 49: 397–403, 2000
Melkko J, Hellevik T, Risteli L, Risteli J, Smedsrød B: Clearance of NH2-terminal propeptides of type I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells. J Exp Med 179: 405–412, 1994
Smedsrød B, Melkko J, Mayer U, Johansson S: Nidogen is a physiological ligand for the scavenger receptor in liver enothelial cells. Atherosclerosis 134: 362, 1997
Nagelkerke F, Havekes L, van Hinsbergh VWM, van Berkel TJC: In vivo and in vitro catabolism of native and biologically modified LDL. FEBS Lett 171: 149–153, 1984
Smedsrød B, Melkko J, Araki N, Sano H, Horiuchi S: Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells. Biochem J 322: 567–573, 1997
Hughes DA, Fraser IP, Gordon S: Murine macrophage scavenger receptor: In vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs. Eur J Immunol 25: 466–473, 1995
Juvet L, Løvdal T, Kjeken R, Berg T, Gjøen T: Role of receptors and endocytosis in hepatic sinusoidal cells. Cells Hepat Sinus 7: 43–48, 1999
Matsumoto K, Sano H, Nagai R, Suzuki H, Kodama T, Yoshida M, Ueda S, Smedsrød B, Horiuch S: Endocytic uptake of advanced glycation end products by mouse liver sinusoidal endothelial cells is mediated by a scavenger receptor distinct from the macrophage scavenger receptor class A. Biochem J 352: 233–240, 2000
Mego JL, Bertini F, McQueen JD: The use of formaldehyde-treated 131I-albumin in the study of digestive vacuoles and some properties of these particles from mouse liver. J Cell Biol 32: 699–707, 1967
Markwell MAK: A new solid-state reagent to iodonate proteins. I. Conditions for the efficient labeling of antiserum. Anal Biochem 125: 427–432, 1982
Pertoft H, Smedrød B: Separation and characterizaton of liver cells. In: TG Pretlow, TP Pretlow (eds). Cell Separation: Methods and Selected Applications, Vol. 4. Academic Press, New York, 1987, pp 1–24
Laakso T, Smedsrød B: Cellular distribution in rat liver of intravenously administered polyacryl starch and chondroitin sulfate microparticles. Int J Pharmaceut 36: 253–262, 1987
Smedsrød B, Pertoft H, Gustafson S, Laurent TC: Scavenger function of the liver endothelial cell. Biochem J 266: 313–327, 1990
Takata K, Horiuchi S, Araki N, Shiga M, Saitoh M, Morino Y: Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins. J Biol Chem 263: 14819–14825, 1988
Smedsrød B, Melkko J, Araki N, Sano H, Horiuchi S: Advanced glycation end products are eliminated by scavenger receptor mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells. Cells Hepat Sinus 6: 378–379, 1997
Blomhoff R, Drevon CA, Eskild W, Helgerud P, Norum KR, Berg T: Clearance of acetyl low density lipoprotein by rat liver endothelial cells. J Biol Chem 259: 8898–8903, 1984
Horiuchi S, Takata K, Murakami M, Morino Y: Receptor-mediated endocytosis of aldehyde-modified proteins by sinusoidal liver cells. J Protein Chem 6: 191–205, 1987
Nagelkerke JF, Barto KP, van Berke TJC: In vivo and in vitro uptake and degradation of acetylated low density lipoprotein by rat liver endothelial, Kupffer, and parenchymal cells. J Biol Chem 258: 12221–12227, 1983
Eskild W, Kindberg GM, Smedsrød B, Blomhoff R, Norum KR, Berg T: Intracellular transport of formaldehyde-treated serum albumin in liver endothelial cells after uptake via scavenger receptors. Biochem J 258: 511–520, 1989
van Oosten M, van de Bilt E, van Berkel TJC, Kuiper J: New scavenger receptor-like receptors for the binding of lipopolysaccharide to liver endothelial and Kupffer cells. Infect Immun 66: 5107–5112, 1998
Kume S, Takeya M, Mori T, Araki N, Suzuki H, Horiuchi S, Kodama T, Miyauchi Y, Takahash K: Immunohistochemical and ultrastructural detection of advanced glycation end products in athersclerotic lesions of human aorta with a novel specific monoclonal antibody. Am J Pathol 147: 654–667, 1995
Ek I, Thunell S, Blomback M: Enhanced in vivo platelet activation in diabetes mellitus. Scand J Haematol 29: 185–191, 1982
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Hansen, B., Melkko, J. & Smedsrød, B. Serum is a rich source of ligands for the scavenger receptor of hepatic sinusoidal endothelial cells. Mol Cell Biochem 229, 63–72 (2002). https://doi.org/10.1023/A:1017919800347
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DOI: https://doi.org/10.1023/A:1017919800347