Human recombinant apolipoprotein E redirects lipopolysaccharide from Kupffer cells to liver parenchymal cells in rats In vivo.
Open accessAbstract
Chylomicrons have been shown to protect mice and rats against a lethal dose of lipopolysaccharide and may serve as a therapeutic means to protect against endotoxemia. However, the requisite of isolation from human lymph hampers pharmaceutical application. Recently, we developed recombinant chylomicrons from commercially available lipids and human recombinant apolipoprotein E. The current study explored the effectiveness of these apoE-enriched emulsions in redirecting LPS from Kupffer cells to liver parenchymal cells. Upon injection into rats, 125I-LPS rapidly and specifically associated with the liver (64.3+/-3.1% of the injected dose) and spleen (4.1+/-0.7%). The uptake of LPS by the spleen was four- to fivefold reduced upon incubation with the apoE-enriched emulsion or free apoE (P < 0.0001), but not with emulsion alone or Lipofundin. Within the liver, 125I-LPS mainly associated with Kupffer cells. The uptake by Kupffer cells was eight- to ninefold reduced by the apoE-enriched emulsion or apoE alone (P < 0.01), and a 19.6-fold increased uptake ratio by liver parenchymal cells over Kupffer cells was observed. The emulsion without apoE had no effect on the in vivo kinetics of LPS. LPS interacted selectively with the apoE moiety of the recombinant chylomicron. Emulsion-associated and free apoE bound approximately two molecules of LPS, possibly by its exposed hydrophilic domain involving arginine residues. We anticipate that the protecting effect of endogenous chylomicrons against LPS-induced endotoxemia may result from the apoE moiety and that human recombinant apoE may serve as a therapeuticum to protect against endotoxemia.
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ApoE was involved in the direct binding of lipopolysaccharide, thereby decreasing the inflammatory response to lipopolysaccharide.
“apoE was involved in the direct binding of lipopolysaccharide, the main toxic component of gram-negative bacteria [ 36], thereby decreasing the inflammatory response to lipopolysaccharide [ 37].”
From ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age (2006) · cites this paper as [36]
The Discussion (page unavailable) reports that apoE binds LPS and redirects it away from Kupffer cells in rats. The Introduction says lipoproteins reduced TNF and inhibited cytokine production, but the paper only suspects apoE is responsible for their protective effect; it does not directly demonstrate that apoE decreases the inflammatory response. (LLM, conf=0.85)
Experimental — accuracy not yet measuredEndotoxin binds directly to APOE.
“Endotoxin binds directly to APOE”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [81]
There is a clear and direct link between APOE variants and endotoxin.
“Thus, there is a clear and direct link between APOE variants and endotoxin.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [81]
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Cites
CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding Protein
Wright, S. D., Ramos, R., Tobias, P. S., Ulevitch, R. J., & Mathison, J. C. (1990) · Science · doi:10.1126/science.1698311 · Cited by 3,986 · see citing works
Pathogenetic Mechanisms of Septic Shock
Epstein, F. H., & Parrillo, J. E. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282008 · Cited by 1,548 · see citing works
Cachectin: More Than a Tumor Necrosis Factor
Epstein, F. H., Beutler, B., & Cerami, A. (1987) · New England Journal of Medicine · doi:10.1056/nejm198702123160705 · Cited by 1,423 · see citing works
Parrillo, J. E., Parker, M. M., Natanson, C., Suffredini, A. F., Danner, R. L., Cunnion, R. E., & Ognibene, F. P. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-3-227 · Cited by 1,188 · see citing works
Waage, A., Brandtzaeg, P., Halstensen, A. I., Kierulf, P., & Espevik, T. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.1.333 · Cited by 1,175 · see citing works
Blouin, A., Bolender, R. P., & Weibel, E. R. (1977) · The Journal of Cell Biology · doi:10.1083/jcb.72.2.441 · Cited by 866 · see citing works
Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides
Morrison, D. C., & Jacobs, D. M. (1976) · Immunochemistry · doi:10.1016/0019-2791(76)90181-6 · Cited by 819 · see citing works
Karkhanis, Y. D., Zeltner, J. Y., Jackson, J. J., & Carlo, D. J. (1978) · Analytical Biochemistry · doi:10.1016/0003-2697(78)90260-9 · Cited by 704 · see citing works
In vivo protection against endotoxin by plasma high density lipoprotein.
Levine, D. M., Parker, T. S., Donnelly, T. M., Walsh, A., & Rubin, A. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.12040 · Cited by 485 · see citing works
Wurfel, M. M., Kunitake, S. T., Lichenstein, H., Kane, J. P., & Wright, S. D. (1994) · The Journal of experimental medicine · doi:10.1084/jem.180.3.1025 · Cited by 442 · see citing works
Mathison, J. C., & Ulevitch, R. J. (1979) · The Journal of Immunology · doi:10.4049/jimmunol.123.5.2133 · Cited by 425 · see citing works
Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo.
Feingold, K. R., & Grünfeld, C. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113046 · Cited by 403 · see citing works
Nagelkerke, J. F., Barto, K. P., & van Berkel, T. J. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44160-3 · Cited by 392 · see citing works
Self-citationPatthy, L., & Smith, E. L. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)41933-9 · Cited by 387 · see citing works
Lactoferrin is a lipid A-binding protein
Appelmelk, B. J., An, Y. Q., Geerts, M., Thijs, B. G., de Boer, H. A., MacLaren, D. M., Graaff, J., & Nuijens, J. H. (1994) · Infection and Immunity · doi:10.1128/iai.62.6.2628-2632.1994 · Cited by 362 · see citing works
Feingold, K., Staprãns, I., Memon, R., Moser, A. H., Shigenaga, J. K., Doerrler, W. T., Dinarello, C. A., & Grünfeld, C. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41334-3 · Cited by 346 · see citing works
Harris, H. W., Grünfeld, C., Kr, F., & Rapp, J. H. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114765 · Cited by 321 · see citing works
Ulevitch, R. J., Johnston, A. R., & Weinstein, D. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109610 · Cited by 298 · see citing works
Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells.
Kawakami, M., Pekala, P. H., Lane, M. D., & Cerami, A. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.3.912 · Cited by 267 · see citing works
Chensue, S. W., Terebuh, P., Remick, D. G., Scales, W. E., & Kunkel, S. L. (1991) · PubMed Central · Cited by 260 · see citing works
Elass, E., Roșeanu, A., Legrand, D., Trif, M., Salmon, V., Motaş, C., Montreuil, J., & Spik, G. (1995) · Biochemical Journal · doi:10.1042/bj3120839 · Cited by 250 · see citing works
Rietschel, E., Gotter, H., Luderitz, O., & Westphal, O. (1972) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1972.tb01899.x · Cited by 241 · see citing works
Recognition of endotoxin by cells leading to transmembrane signaling
Ulevitch, R. J., & Tobias, P. S. (1994) · Current Opinion in Immunology · doi:10.1016/0952-7915(94)90043-4 · Cited by 238 · see citing works
Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo.
Machnicki, M., Zimecki, M., & Zagulski, T. (1993) · Europe PMC (PubMed Central) · Cited by 232 · see citing works
Harris, H. W., Grünfeld, C., Feingold, K. R., Read, T. E., Kane, J. P., Jones, A. L., Eichbaum, E. B., Bland, G. F., & Rapp, J. H. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116259 · Cited by 214 · see citing works
Parker, T. S., Levine, D. M., Chang, J. C., Laxer, J., Coffin, C. C., & Rubin, A. L. (1995) · Infection and Immunity · doi:10.1128/iai.63.1.253-258.1995 · Cited by 211 · see citing works
Uptake by liver cells of endotoxin following its intravenous injection.
Dj, R., van der Meulen, J., Brouwer, A., Mj, H., Mauw, B. J., Jc, V. D. P., & Wisse, E. (1981) · PubMed · Cited by 188 · see citing works
Clearance Capacity of Rat Liver Kupffer, Endothelial, and Parenchymal Cells
Dalen, D. P. P.-V., Brouwer, A., & Knook, D. L. (1981) · Gastroenterology · doi:10.1016/s0016-5085(81)80009-1 · Cited by 186 · see citing works
Lenten, B. J. V., Fogelman, A. M., Haberland, M. E., & Edwards, P. A. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.8.2704 · Cited by 185 · see citing works
Flegel, W. A., Baumstark, M. W., Weinstock, C., Berg, A., & Northoff, H. (1993) · Infection and Immunity · doi:10.1128/iai.61.12.5140-5146.1993 · Cited by 169 · see citing works
Metabolism of protein-free lipid emulsion models of chylomicrons in rats
Redgrave, T. G., & Maranhão, R. C. (1985) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(85)90036-0 · Cited by 162 · see citing works
In vitro inactivation of bacterial endotoxin by human lipoproteins and apolipoproteins
Emancipator, K., Csákó, G., & Elin, R. J. (1992) · Infection and Immunity · doi:10.1128/iai.60.2.596-601.1992 · Cited by 154 · see citing works
Rensen, P. C. N., van Dijk, M. C. M., Havenaar, E. C., Bijsterbosch, M. K., Kruijt, J. K., & van Berkel, T. J. C. (1995) · Nature Medicine · doi:10.1038/nm0395-221 · Cited by 147 · see citing works
Self-citationRensen, P. C. N., & van Berkel, T. J. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.14791 · Cited by 144 · see citing works
Self-citationTime course of cellular distribution of endotoxin in liver, lungs and kidneys of rats.
Freudenberg, M. A., Freudenberg, N., & Galanos, C. (1982) · PubMed · Cited by 143 · see citing works
Hypertriglyceridemia Produced by Endotoxin: Role of Impaired Triglyceride Disposal Mechanisms
Kaufmann, R. L., Matson, C. F., & Beisel, W. R. (1976) · The Journal of Infectious Diseases · doi:10.1093/infdis/133.5.548 · Cited by 114 · see citing works
Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion
Wolfe, R. R., Shaw, J. H., & Durkot, M. J. (1985) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1985.248.6.e732 · Cited by 112 · see citing works
Miyazawa, K., Mantel, C., Lü, L., Morrison, D. C., & Broxmeyer, H. E. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.2.723 · Cited by 103 · see citing works
The preparation and characterization of a radioiodinated bacterial lipopolysaccharide
Ulevitch, R. J. (1978) · Immunochemistry · doi:10.1016/0161-5890(78)90144-x · Cited by 103 · see citing works
Binding of Salmonella typhimurium lipopolysaccharides to rat high-density lipoproteins
Munford, R. S., Hall, C. L., & Dietschy, J. M. (1981) · Infection and Immunity · doi:10.1128/iai.34.3.835-843.1981 · Cited by 101 · see citing works
Park, C. T., & Wright, S. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.18054 · Cited by 98 · see citing works
Cohen, M. S., Mao, J., Rasmussen, G. T., Serody, J. S., & Britigan, B. E. (1992) · The Journal of Infectious Diseases · doi:10.1093/infdis/166.6.1375 · Cited by 90 · see citing works
Vogel, T., Weisgraber, K. H., Zeevi, M. I., Ben-Artzi, H., Levanon, A. Z., Rall, S. C., Innerarity, T. L., Hui, D. Y., Taylor, J. M., & Kanner, D. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.24.8696 · Cited by 88 · see citing works
Chylomicrons enhance endotoxin excretion in bile
Read, T. E., Harris, H. W., Grünfeld, C., Feingold, K. R., Calhoun, M. C., Kane, J. P., & Rapp, J. H. (1993) · Infection and Immunity · doi:10.1128/iai.61.8.3496-3502.1993 · Cited by 73 · see citing works
Characteristics of chylomicron remnant uptake into rat liver
Huettinger, M., Retzek, H., Eder, M., & Goldenberg, H. (1988) · Clinical Biochemistry · doi:10.1016/s0009-9120(88)80093-6 · Cited by 72 · see citing works
High density lipoprotein catabolism before and after partial hepatectomy
van Tol, A., van Gent, T., Hooft, F. M. V., & Vlaspolder, F. (1978) · Atherosclerosis · doi:10.1016/0021-9150(78)90172-7 · Cited by 71 · see citing works
Bijsterbosch, M. K., Ziere, G. J., & van Berkel, T. J. (1989) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09320-4 · Cited by 68 · see citing works
Self-citationThe interaction in vivo of transferrin and asialotransferrin with liver cells
van Berkel, T. J. C., Dekker, C. J., Kruijt, J. K., & van Eijk, H. G. (1987) · Biochemical Journal · doi:10.1042/bj2430715 · Cited by 55 · see citing works
Self-citationEffect of hypertriglyceridemia on endotoxin responsiveness in humans
van der Poll, T., Braxton, C. C., Coyle, S. M., Boermeester, M. A., Wang, J.-C., Jansen, P. M., Montegut, W. J., Calvano, S. E., Hack, C. E., & Lowry, S. F. (1995) · Infection and Immunity · doi:10.1128/iai.63.9.3396-3400.1995 · Cited by 55 · see citing works
Lactoferrin Is a Lipid A-Binding Protein
(1994) · Infection and Immunity · doi:10.1128/iai.62.10.4695-4695.1994 · Cited by 8 · see citing works
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Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock
van Amersfoort, E. S., van Berkel, T. J. C., & Kuiper, J. (2003) · Clinical Microbiology Reviews · doi:10.1128/cmr.16.3.379-414.2003 · Cited by 750 · see citing works
Self-citationDyslipidemia and inflammation: an evolutionary conserved mechanism
Esteve, E., Ricart, W., & Fernández-Real, J. M. (2005) · Clinical Nutrition · doi:10.1016/j.clnu.2004.08.004 · Cited by 492 · see citing works
The endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457 · see citing works
Apolipoprotein E Induces Antiinflammatory Phenotype in Macrophages
Baitsch, D., Bock, H. H., Engel, T., Telgmann, R., Müller‐Tidow, C., Varga, G., Bot, M., Herz, J., Robenek, H., von Eckardstein, A., et al. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.222745 · Cited by 361 · see citing works
Gut microbiota and diabetes: from pathogenesis to therapeutic perspective
Burcelin, R., Sérino, M., Chabo, C., Blasco‐Baqué, V., & Amar, J. (2011) · Acta Diabetologica · doi:10.1007/s00592-011-0333-6 · Cited by 256 · see citing works
Whitten, M. M. A., Tew, I., Lee, B. L., & Ratcliffe, N. A. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.4.2177 · Cited by 222 · see citing works
Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting
Rensen, P. C. N., de Vrueh, R. L. A., Kuiper, J., Bijsterbosch, M. K., Biessen, E. A. L., & van Berkel, T. J. C. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00109-0 · Cited by 217 · see citing works
Self-citationde Bont, N., Netea, M. G., Demacker, P. N. M., Verschueren, I., Kullberg, B. J., van Dijk, K. W., van der Meer, J. W. M., & Stalenhoef, A. F. H. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32147-7 · Cited by 210 · see citing works
APOε4 is associated with enhanced in vivo innate immune responses in human subjects
Gale, S. C., Gao, L., Mikacenic, C., Coyle, S. M., Rafaels, N., Murray Dudenkov, T., Madenspacher, J. H., Draper, D. W., Ge, W., Aloor, J. J., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.01.032 · Cited by 202 · see citing works
Lipopolysaccharide (LPS)-Binding Protein Mediates LPS Detoxification by Chylomicrons
Vreugdenhil, A. C. E., Rousseau, C. H., Härtung, T., Greve, J. W. M., Veer, C. V. ′., & Buurman, W. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1399 · Cited by 206 · see citing works
Wu, A., Hinds, C., & Thiemermann, C. (2004) · Shock · doi:10.1097/01.shk.0000111661.09279.82 · Cited by 199 · see citing works
Gut microbiota and immune crosstalk in metabolic disease
Burcelin, R. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.05.016 · Cited by 191 · see citing works
Guerville, M., & Boudry, G. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00098.2016 · Cited by 189 · see citing works
Apolipoprotein E Protects Against Bacterial Lipopolysaccharide-induced Lethality
Van Oosten, M., Rensen, P. C. N., Van Amersfoort, E. S., Van Eck, M., Van Dam, A.-M., Brevé, J. J. P., Vogel, T., Panet, A., Van Berkel, T. J. C., & Kuiper, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009915200 · Cited by 186 · see citing works
Self-citationLipoproteins in inflammation and sepsis. I. Basic science
Murch, O., Collin, M., Hinds, C., & Thiemermann, C. (2006) · Intensive Care Medicine · doi:10.1007/s00134-006-0432-y · Cited by 179 · see citing works
Apolipoprotein E Suppresses the Type I Inflammatory Response In Vivo
Ali, K., Middleton, M. K., Puré, E., & Rader, D. J. (2005) · Circulation Research · doi:10.1161/01.res.0000187467.67684.43 · Cited by 179 · see citing works
Barlage, S., Gnewuch, C., Liebisch, G., Wolf, Z., Audebert, F., Glück, T., Fröhlich, D., Krämer, B. K., Rothe, G., & Schmitz, G. (2009) · Intensive Care Medicine · doi:10.1007/s00134-009-1609-y · Cited by 174 · see citing works
Cuaz‐Pérolin, C., Billiet, L., Baugé, E., Copin, C., Scott‐Algara, D., Genze, F., Büchele, B., Syrovets, T., Simmet, T., & Rouis, M. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.155606 · Cited by 170 · see citing works
Cai, L., Ji, A., de Beer, F. C., Tannock, L. R., & van der Westhuyzen, D. R. (2008) · Journal of Clinical Investigation · doi:10.1172/jci31539 · Cited by 167 · see citing works
Vreugdenhil, A. C. E., Snoek, A. M. P., Veer, C. V. ′., Greve, J.-W. M., & Buurman, W. A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10832 · Cited by 166 · see citing works
Ostos, M. A., Recalde, D., Zakin, M. M., & Scott‐Algara, D. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02692-3 · Cited by 152 · see citing works
Changes in the concentration and composition of plasma lipoproteins during the acute phase response
Carpentier, Y. A., & Scruel, O. (2002) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/00075197-200203000-00006 · Cited by 148 · see citing works
Apolipoproteins modulate the inflammatory response to lipopolysaccharide
Berbée, J. F. P., Havekes, L. M., & Rensen, P. C. N. (2005) · Journal of Endotoxin Research · doi:10.1179/096805105x35215 · Cited by 145 · see citing works
Self-citationLipoproteins inhibit macrophage activation by lipoteichoic acid
Grünfeld, C., Marshall, M. K., Shigenaga, J. K., Moser, A. H., Tobias, P. S., & Feingold, K. R. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33363-0 · Cited by 143 · see citing works
Immuno-microbiota cross and talk: The new paradigm of metabolic diseases
Burcelin, R., Garidou, L., & Pomié, C. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2011.11.011 · Cited by 142 · see citing works
The endotoxin hypothesis of Alzheimer’s disease
Brown, G. C., & Heneka, M. T. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00722-y · Cited by 140 · see citing works
Yao, X., Gordon, E. M., Figueroa, D. M., Barochia, A. V., & Levine, S. J. (2016) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0060tr · Cited by 132 · see citing works
ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age
Mooijaart, S. P., Berbée, J. F. P., van Heemst, D., Havekes, L. M., de Craen, A. J. M., Slagboom, P. E., Rensen, P. C. N., & Westendorp, R. G. J. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030176 · Cited by 129 · see citing works
Self-citationKitchens, R. L., Thompson, P. A., Munford, R. S., & O’Keefe, G. E. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m300228-jlr200 · Cited by 123 · see citing works
Recalde, D., Ostos, M. A., Badell, E., García-Otín, A. L., Pidoux, J., Castro, G. R., Zakin, M. M., & Scott‐Algara, D. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000119353.03690.22 · Cited by 116 · see citing works
Detoxifying endotoxin: time, place and person
Munford, R. S. (2005) · Journal of Endotoxin Research · doi:10.1179/096805105x35161 · Cited by 150 · see citing works
Triglyceride-Rich Lipoproteins as Agents of Innate Immunity
Barcia, A. M., & Harris, H. W. (2005) · Clinical Infectious Diseases · doi:10.1086/432005 · Cited by 97 · see citing works
Yao, X., Fredriksson, K., Yu, Z., Xu, X., Raghavachari, N., Keeran, K. J., Nugent, G. Z., Kwak, M., Amar, M. J., Remaley, A. T., et al. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201002-0308oc · Cited by 95 · see citing works
Reduction of Circulating Cholesterol and Apolipoprotein Levels during Sepsis
Fraunberger, P., Schaefer, S., Werdan, K., Walli, A. K., & Seidel, D. (1999) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1999.059 · Cited by 94 · see citing works
Review: The lipemia of sepsis: triglyceride-rich lipoproteins as agents of innate immunity
Harris, H. W., Gosnell, J. E., & Kumwenda, Z. L. (2000) · Journal of Endotoxin Research · doi:10.1177/09680519000060060301 · Cited by 93 · see citing works
On the role and fate of LPS-dephosphorylating activity in the rat liver
Tuin, A., der Vlag, A. H., van Loenen-Weemaes, A. M., Meijer, D. K. F., & Poelstra, K. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00147.2005 · Cited by 91 · see citing works
Advances in Intravenous Lipid Emulsions
Carpentier, Y., & Dupont, I. E. (2000) · World Journal of Surgery · doi:10.1007/s002680010267 · Cited by 83 · see citing works
Endogenous carriers and ligands in non-immunogenic site-specific drug delivery
Vyas, S. P., & Sihorkar, V. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00067-3 · Cited by 82 · see citing works
Jiang, Q., DeTolla, L. J., van Rooijen, N., Singh, I. S., Fitzgerald, B., Lipsky, M. M., Kane, A. S., Cross, A. S., & Hasday, J. D. (1999) · Infection and Immunity · doi:10.1128/iai.67.4.1539-1546.1999 · Cited by 79 · see citing works
Berbée, J. F. P., van der Hoogt, C. C., Kleemann, R., Schippers, E. F., Kitchens, R. L., van Dissel, J. T., Bakker‐Woudenberg, I. A. J. M., Havekes, L. M., & Rensen, P. C. N. (2006) · The FASEB Journal · doi:10.1096/fj.05-5639fje · Cited by 81 · see citing works
Self-citationLipopolysaccharide-binding molecules: transporters, blockers and sensors
Chaby, R. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4020-4 · Cited by 79 · see citing works
Endothelial FN (Fibronectin) Deposition by α5β1 Integrins Drives Atherogenic Inflammation
Al‐Yafeai, Z., Yurdagul, A., Peretik, J. M., Alfaidi, M., Murphy, P. A., & Orr, A. W. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311705 · Cited by 78 · see citing works
Learning from biology: synthetic lipoproteins for drug delivery
Huang, H., Cruz, W., Chen, J., & Zheng, G. (2014) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1308 · Cited by 75 · see citing works
Apolipoprotein E‐deficient mice have an impaired immune response to Klebsiella pneumoniae
Bont, D., Netea, Demacker, Kullberg, Meer, V. D., & Stalenhoef (2000) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2000.00715.x · Cited by 71 · see citing works
Infection and Alzheimer's Disease: The APOE ε4 Connection and Lipid Metabolism
Urosevic, N., & Martins, R. N. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13407 · Cited by 68 · see citing works
Hepatic uptake and deacylation of the LPS in bloodborne LPS-lipoprotein complexes
Shao, B., Munford, R. S., Kitchens, R. L., & Varley, A. W. (2012) · Innate Immunity · doi:10.1177/1753425912442431 · Cited by 65 · see citing works
Association of low-density lipoprotein receptor polymorphisms and outcome of hepatitis C infection
Hennig, B. J., Hellier, S. C., Frodsham, A. J., Zhang, L., Klenerman, P., Knapp, S., Wright, M., Thomas, H. C., Thursz, M. R., & Hill, A. V. S. (2002) · Genes and Immunity · doi:10.1038/sj.gene.6363883 · Cited by 65 · see citing works
Li, L., Thompson, P. A., & Kitchens, R. L. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800172-jlr200 · Cited by 63 · see citing works
Walley, K. R., Francis, G. A., Opal, S. M., Stein, E. A., Russell, J. A., & Boyd, J. H. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201505-0876ci · Cited by 58 · see citing works
Endogenous lipoproteins impact the response to endotoxin in humans
Harris, H. W., Johnson, J. A., & Wigmore, S. J. (2002) · Critical Care Medicine · doi:10.1097/00003246-200201000-00004 · Cited by 56 · see citing works
Kitchens, R. L., & Thompson, P. A. (2003) · Journal of Endotoxin Research · doi:10.1177/09680519030090020701 · Cited by 52 · see citing works
de Azevedo, O. G. R., Bolick, D. T., Roche, J. K., Pinkerton, R., Lima, A. Â. M., Vitek, M. P., Warren, C. A., Oriá, R. B., & Guerrant, R. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089562 · Cited by 51 · see citing works
de Haas, C. D., van der Zee, R., Benaissa-Trouw, B., van Kessel, K. V., Verhoef, J., & van Strijp, J. V. (1999) · Infection and Immunity · doi:10.1128/iai.67.6.2790-2796.1999 · Cited by 51 · see citing works
Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis
de Azevedo, O. G. R., Oliveira, R. A. C., Oliveira, B. C., Zaja‐Milatovic, S., de Araújo, C. V., Wong, D. V. T., Costa, T. B., Lucena, H. B. M., Lima‐Júnior, R. C. P., Ribeiro, R. A., et al. (2012) · BMC Gastroenterology · doi:10.1186/1471-230x-12-35 · Cited by 45 · see citing works
Goldfarb, R. D., Parker, T. S., Levine, D. M., Glock, D., Akhter, I., Alkhudari, A., McCarthy, R. J., David, E. M., Gordon, B. R., Saal, S. D., et al. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00285.2002 · Cited by 44 · see citing works
Host defenses against metabolic endotoxaemia and their impact on lipopolysaccharide detection
Faraj, T. A., McLaughlin, C. L., & Erridge, C. (2017) · International Reviews of Immunology · doi:10.1080/08830185.2017.1280483 · Cited by 44 · see citing works
Shao, Y., Zhao, T., Zhang, W., He, J., Lu, F., Cai, Y., Lai, Z., Wei, N., Liang, C., Liu, L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-72616-0 · Cited by 42 · see citing works
Thompson, P. A., Berbée, J. F. P., Rensen, P. C. N., & Kitchens, R. L. (2008) · Innate Immunity · doi:10.1177/1753425908099171 · Cited by 41 · see citing works
Self-citationA Novel Role for CETP as Immunological Gatekeeper: Raising HDL to Cure Sepsis?
Blauw, L. L., Wang, Y., van Dijk, K. W., & Rensen, P. C. N. (2020) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.01.003 · Cited by 40 · see citing works
Self-citationRomanovsky, A. A., Ivanov, A. I., Lenczowski, M. J. P., KULCHITSKY, V. A., van Dam, A., Poole, S., HOMER, L. D., & Tilders, F. J. H. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00232-0 · Cited by 39 · see citing works
Hara, T., Ishida, T., Kojima, Y., Tanaka, H., Yasuda, T., Shinohara, M., Toh, R., & Hirata, K. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m008417 · Cited by 38 · see citing works
Thompson, P. A., Gauthier, K. C., Varley, A. W., & Kitchens, R. L. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m007435 · Cited by 36 · see citing works
Saita, D., Ferrarese, R., Foglieni, C., Esposito, A., Canu, T., Perani, L., Ceresola, E. R., Visconti, L. M., Burioni, R., Clementi, M., et al. (2016) · Scientific Reports · doi:10.1038/srep29353 · Cited by 36 · see citing works
Triglycerides Potentiate the Inflammatory Response in Rat Kupffer Cells
Budick-Harmelin, N., Dudás, J., Demuth, J. E., Madar, Z., Ramadori, G. P., & Tirosh, O. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1876 · Cited by 35 · see citing works
APOE Genotype Affects Outcome in a Murine Model of Sepsis: Implications for a New Treatment Strategy
Wang, H., Christensen, D. J., Vitek, M. P., Sullivan, P. M., & Laskowitz, D. T. (2009) · Anaesthesia and Intensive Care · doi:10.1177/0310057x0903700111 · Cited by 34 · see citing works
Endotoxin promotes preferential periportal upregulation of VLDL secretion in the rat liver
Aspichueta, P., Pérez, S., Ochoa, B., & Fresnedo, O. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500003-jlr200 · Cited by 32 · see citing works
Araújo, C. V., Lazzarotto, C. R., de Aquino, C. C., Figueiredo, Í. L., Costa, T. B., Alves, L. G. R. D. D. S. E., Ribeiro, R. A., Bertolini, L. R., Lima, A. Â. M., Brito, G. A. D. C., et al. (2015) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20144360 · Cited by 29 · see citing works
Yang, Y., Fu, Q., Zhou, T., Li, Y., Liu, S., Zeng, Q., Wang, X., Jin, Y., Tian, C., Qin, Z., et al. (2016) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2016.09.007 · Cited by 28 · see citing works
Liver X Receptor Alpha Associates With Human Life Span
Mooijaart, S. P., Kuningas, M., Westendorp, R. G. J., Houwing‐Duistermaat, J. J., Slagboom, P. E., Rensen, P. C. N., & van Heemst, D. (2007) · The Journals of Gerontology Series A · doi:10.1093/gerona/62.4.343 · Cited by 28 · see citing works
Self-citationHepatocyte-specific IKK-β activation enhances VLDL-triglyceride production in APOE*3-Leiden mice
van Diepen, J. A., Wong, M. C., Guigas, B., Bos, J. E., Stienstra, R., Hodson, L., Shoelson, S. E., Berbée, J. F. P., Rensen, P. C. N., Romijn, J. A., et al. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m010405 · Cited by 26 · see citing works
Self-citationPlasma Apolipoprotein CI Protects Against Mortality From Infection in Old Age
Berbée, J. F. P., Mooijaart, S. P., de Craen, A. J. M., Havekes, L. M., van Heemst, D., Rensen, P. C. N., & Westendorp, R. G. J. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.2.122 · Cited by 25 · see citing works
Self-citationTyrosine fluorescence analysis of apolipophorin III–lipopolysaccharide interaction
Leon, L. J., Pratt, C. C., Vásquez, L. J., & Weers, P. M. M. (2006) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.05.009 · Cited by 24 · see citing works
An expanding role for apolipoprotein E in sepsis and inflammation
Chuang, K., Elford, E. L., Tseng, J., Leung, B., & Harris, H. W. (2010) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2009.10.017 · Cited by 24 · see citing works
NKT Cells: The Culprits of Sepsis?
Leung, B., & Harris, H. W. (2010) · Journal of Surgical Research · doi:10.1016/j.jss.2010.09.038 · Cited by 23 · see citing works
Schippers, E. F., Berbée, J. F. P., Disseldorp, I. M. L.-V., Versteegh, M. I. M., Havekes, L. M., Rensen, P. C. N., & van Dissel, J. T. (2008) · Intensive Care Medicine · doi:10.1007/s00134-008-1077-9 · Cited by 22 · see citing works
Self-citationBas, S., James, R. W., & Gabay, C. (2010) · BMC Immunology · doi:10.1186/1471-2172-11-46 · Cited by 19 · see citing works
[Retracted] NKT Cells in Sepsis
Leung, B., & Harris, H. W. (2010) · Journal of Immunology Research · doi:10.1155/2010/414650 · Cited by 19 · see citing works
RetractedMicrobiote intestinal et dialogue immunitaire au cours de la maladie métabolique
Burcelin, R. (2017) · Biologie Aujourd hui · doi:10.1051/jbio/2017008 · Cited by 18 · see citing works
Lanza‐Jacoby, S., Miller, S., Jacob, S., Heumann, D., Minchenko, О. H., & Flynn, J. T. (2003) · Journal of Endotoxin Research · doi:10.1177/09680519030090060701 · Cited by 18 · see citing works
Clinical use of lipid emulsions
Dupont, I. E., & Carpentier, Y. (1999) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-199903000-00008 · Cited by 18 · see citing works
Rathnayake, S. S., Mirheydari, M., Schulte, A. T., Gillahan, J. E., Gentit, T., Phillips, A., Okonkwo, R. K., Burger, K. N. J., Mann, E. K., Vaknin, D., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2013.09.020 · Cited by 16 · see citing works
Kulminski, A. M., Barochia, A. V., Loika, Y., Raghavachari, N., Arbeev, K. G., Wojczynski, M. K., Thyagarajan, B., Vardarajan, B. N., Christensen, K., Yashin, A. I., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206873 · Cited by 16 · see citing works
Modulation of apolipoprotein E and interleukin-1β in the aging liver
Gee, J. R., Ding, Q., & Keller, J. N. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.01.010 · Cited by 16 · see citing works
Apolipoproteins as context-dependent regulators of lung inflammation
Figueroa, D. M., Gordon, E. M., Yao, X., & Levine, S. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813553-2.00013-0 · Cited by 14 · see citing works
Freitas, R. S., Roque, C. R., Matos, G. A., Belayev, L., de Azevedo, O. G. R., Alvarez-Leite, J. I., Guerrant, R. L., & Oriá, R. B. (2021) · Nutrition Reviews · doi:10.1093/nutrit/nuab063 · Cited by 13 · see citing works
Sharifov, O. F., Nayyar, G., Ternovoi, V. V., Palgunachari, M. N., Garber, D. W., Anantharamaiah, G. M., & Gupta, H. (2013) · Innate Immunity · doi:10.1177/1753425913514621 · Cited by 12 · see citing works
Fuijkschot, W. W., Morrison, M. C., Zethof, I. P. A., Krijnen, P. A. J., Kleemann, R., Niessen, H. W. M., & Smulders, Y. M. (2017) · Shock · doi:10.1097/shk.0000000000001026 · Cited by 11 · see citing works
Effect of LPS on basal and induced apo E secretion by 25‐OH chol and 9cRA in differentiated CaCo‐2
Piquer, B. R., Nazih, H., Neunlist, M., Huvelin, J., & Bard, J. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10786 · Cited by 11 · see citing works
Bazaz, R., Marriott, H. M., Wright, C., Chamberlain, J., West, L. E., Gelsthorpe, C., Heath, P. R., Maleki-Dizaji, A., Francis, S., & Dockrell, D. H. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1090550 · Cited by 10 · see citing works
High-density lipoprotein: a biomarker and therapeutic target in sepsis
Li, M., Barros-Pinkelnig, M., Arbous, M. S., Christoffersen, C., Rensen, P. C. N., & Kooijman, S. (2025) · Critical Care · doi:10.1186/s13054-025-05702-2 · Cited by 9 · see citing works
Self-citationFleischer, J. G., Rossignol, D., Francis, G. A., Chan, T., Lynn, M., & Wasan, K. M. (2011) · Innate Immunity · doi:10.1177/1753425910394395 · Cited by 9 · see citing works
Induction of cytokine tolerance requires internalization of Chylomicron-Bound LPS into hepatocytes
Kasravi, F. B., Brecht, W. J., Weisgraber, K. H., & Harris, H. W. (2003) · Journal of Surgical Research · doi:10.1016/s0022-4804(03)00197-5 · Cited by 9 · see citing works
Microbiota and Alzheimer’s disease: mechanistic insights from a multi-organ perspective
Liao, J., Mou, H., Luo, S., Shen, L., & Jiao, B. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00541-9 · Cited by 10 · see citing works
Potential of Lipoprotein-Based Nanoparticulate Formulations for the Treatment of Eye Diseases
Fukuda, R., & Murakami, T. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00858 · Cited by 8 · see citing works
Hoekstra, M., van der Sluis, R. J., Hildebrand, R. B., Lammers, B., Zhao, Y., Praticò, D., van Berkel, T. J. C., Rensen, P. C. N., Kooijman, S., Jauhiainen, M., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313862 · Cited by 8 · see citing works
Self-citationLipoprotein-bound LPS induces cytokine tolerance in hepatocytes
Harris, H. W., & Kasravi, F. B. (2003) · Journal of Endotoxin Research · doi:10.1177/09680519030090010501 · Cited by 7 · see citing works
The effect of poloxamer 407 on the functional properties of HDL in mice
Yasuda, T., Johnston, T. P., Shinohara, M., Inoue, M., & Ishida, T. (2012) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.2011.01444.x · Cited by 6 · see citing works
Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock
van Amersfoort, E. S., & Kuiper, J. (2007) · CRC Press eBooks · doi:10.3109/9781420020595-21 · Cited by 6 · see citing works
Self-citationAkahane, S., Matsuura, H., Kaido, T., Usami, Y., Ishimine, N., Uehara, T., & Yamauchi, K. (2024) · Biological Chemistry · doi:10.1515/hsz-2024-0018 · Cited by 5 · see citing works
Apolipoprotein E3 and E4 isoforms exhibit differing effects in countering endotoxins
Puthia, M., Marzinek, J. K., Veselá, K., Larsson, A., Schmidtchen, A., Bond, P. J., & Petrlová, J. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108236 · Cited by 5 · see citing works
- Authors
- Rensen, P. C., Oosten, M., Bilt, E., Eck, M., Kuiper, J., & Berkel, T. J.
- Affiliations
- Leiden University (NL)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-05-15
- Volume
- 99
- Issue
- 10
- Pages
- 2438-2445
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508084
- OpenAlex
- W2044756436
- Cited by
- 113
- References
- 50
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 4
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- apolipoprotein E, lipopolysaccharide, endotoxemia, Kupffer cells, liver parenchymal cells, spleen, arginine residues
- MeSH terms
- Animals, Apolipoproteins E, Drug Combinations, Emulsions, Humans, Iodine Radioisotopes, Kupffer Cells, Lipopolysaccharides, Liver, Male, Metabolic Clearance Rate, Phospholipids, Recombinant Proteins, Sorbitol, Spleen, Tissue Distribution, Rats, Wistar, Mice, Rats
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