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J Clin Invest. Apr 1990; 85(4): 1260–1266.
PMCID: PMC296561

Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.

Abstract

The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL.

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  • Morton RE, West GA, Hoff HF. A low density lipoprotein-sized particle isolated from human atherosclerotic lesions is internalized by macrophages via a non-scavenger-receptor mechanism. J Lipid Res. 1986 Nov;27(11):1124–1134. [PubMed]
  • Hoff HF, Gaubatz JW. Isolation, purification, and characterization of a lipoprotein containing Apo B from the human aorta. Atherosclerosis. 1982 Apr;42(2-3):273–297. [PubMed]
  • Palinski W, Rosenfeld ME, Ylä-Herttuala S, Gurtner GC, Socher SS, Butler SW, Parthasarathy S, Carew TE, Steinberg D, Witztum JL. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1372–1376. [PMC free article] [PubMed]
  • Nishigaki I, Hagihara M, Tsunekawa H, Maseki M, Yagi K. Lipid peroxide levels of serum lipoprotein fractions of diabetic patients. Biochem Med. 1981 Jun;25(3):373–378. [PubMed]
  • Higuchi Y. Lipid peroxides and alpha-tocopherol in rat streptozotocin-induced diabetes mellitus. Acta Med Okayama. 1982 Jun;36(3):165–175. [PubMed]
  • Chisolm GM, 3rd, Morel DW. Lipoprotein oxidation and cytotoxicity: effect of probucol on streptozotocin-treated rats. Am J Cardiol. 1988 Jul 25;62(3):20B–26B. [PubMed]
  • Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshima A, Yoshida H, Kawai C. Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5928–5931. [PMC free article] [PubMed]
  • Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7725–7729. [PMC free article] [PubMed]
  • Gerrity RG, Naito HK, Richardson M, Schwartz CJ. Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages. Am J Pathol. 1979 Jun;95(3):775–792. [PMC free article] [PubMed]
  • Faggiotto A, Ross R, Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis. 1984 Jul-Aug;4(4):323–340. [PubMed]
  • Morel DW, DiCorleto PE, Chisolm GM. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis. 1984 Jul-Aug;4(4):357–364. [PubMed]
  • Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3883–3887. [PMC free article] [PubMed]
  • Heinecke JW, Rosen H, Chait A. Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest. 1984 Nov;74(5):1890–1894. [PMC free article] [PubMed]
  • Cathcart MK, Morel DW, Chisolm GM., 3rd Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J Leukoc Biol. 1985 Aug;38(2):341–350. [PubMed]
  • Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. [PubMed]
  • Berliner JA, Territo M, Almada L, Carter A, Shafonsky E, Fogelman AM. Monocyte chemotactic factor produced by large vessel endothelial cells in vitro. Arteriosclerosis. 1986 May-Jun;6(3):254–258. [PubMed]
  • Fogelman AM, Elahi F, Sykes K, Van Lenten BJ, Territo MC, Berliner JA. Modification of the Recalde method for the isolation of human monocytes. J Lipid Res. 1988 Sep;29(9):1243–1247. [PubMed]
  • Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed]
  • Kosugi K, Morel DW, DiCorleto PE, Chisolm GM. Toxicity of oxidized low-density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle. J Cell Physiol. 1987 Mar;130(3):311–320. [PubMed]
  • Sevanian A, McLeod LL. Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase. J Biol Chem. 1986 Jan 5;261(1):54–59. [PubMed]
  • Sevanian A, McLeod LL. Cholesterol autoxidation in phospholipid membrane bilayers. Lipids. 1987 Sep;22(9):627–636. [PubMed]
  • Sevanian A, Kim E. Phospholipase A2 dependent release of fatty acids from peroxidized membranes. J Free Radic Biol Med. 1985;1(4):263–271. [PubMed]
  • BARTLETT GR. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed]
  • Pawlowski NA, Abraham EL, Pontier S, Scott WA, Cohn ZA. Human monocyte-endothelial cell interaction in vitro. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8208–8212. [PMC free article] [PubMed]
  • Lee DM. Malondialdehyde formation in stored plasma. Biochem Biophys Res Commun. 1980 Aug 29;95(4):1663–1672. [PubMed]
  • Baker DP, Van Lenten BJ, Fogelman AM, Edwards PA, Kean C, Berliner JA. LDL, scavenger, and beta-VLDL receptors on aortic endothelial cells. Arteriosclerosis. 1984 May-Jun;4(3):248–255. [PubMed]
  • Quinn MT, Parthasarathy S, Steinberg D. Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2805–2809. [PMC free article] [PubMed]
  • Pohlman TH, Stanness KA, Beatty PG, Ochs HD, Harlan JM. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol. 1986 Jun 15;136(12):4548–4553. [PubMed]
  • Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. [PMC free article] [PubMed]
  • Parthasarathy S, Steinbrecher UP, Barnett J, Witztum JL, Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 May;82(9):3000–3004. [PMC free article] [PubMed]
  • Gray MF, Lawrie TD, Brooks CJ. Isolation and identification of cholesterol -oxide and other minor sterols in human serum. Lipids. 1971 Nov;6(11):836–843. [PubMed]
  • Territo MC, Berliner JA, Almada L, Ramirez R, Fogelman AM. Beta-very low density lipoprotein pretreatment of endothelial monolayers increases monocyte adhesion. Arteriosclerosis. 1989 Nov-Dec;9(6):824–828. [PubMed]
  • Endemann G, Pronzcuk A, Friedman G, Lindsey S, Alderson L, Hayes KC. Monocyte adherence to endothelial cells in vitro is increased by beta-VLDL. Am J Pathol. 1987 Jan;126(1):1–6. [PMC free article] [PubMed]
  • Fox PL, Chisolm GM, DiCorleto PE. Lipoprotein-mediated inhibition of endothelial cell production of platelet-derived growth factor-like protein depends on free radical lipid peroxidation. J Biol Chem. 1987 May 5;262(13):6046–6054. [PubMed]
  • Harlan JM, Harker LA, Reidy MA, Gajdusek CM, Schwartz SM, Striker GE. Lipopolysaccharide-mediated bovine endothelial cell injury in vitro. Lab Invest. 1983 Mar;48(3):269–274. [PubMed]
  • Quinn MT, Parthasarathy S, Fong LG, Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci U S A. 1987 May;84(9):2995–2998. [PMC free article] [PubMed]
  • Valente AJ, Graves DT, Vialle-Valentin CE, Delgado R, Schwartz CJ. Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry. 1988 May 31;27(11):4162–4168. [PubMed]
  • Mazzone T, Jensen M, Chait A. Human arterial wall cells secrete factors that are chemotactic for monocytes. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5094–5097. [PMC free article] [PubMed]
  • Matsushima K, Larsen CG, DuBois GC, Oppenheim JJ. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med. 1989 Apr 1;169(4):1485–1490. [PMC free article] [PubMed]

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