• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Feb 1990; 87(3): 904–908.
PMCID: PMC53377

Oxidized low density lipoprotein induces differentiation and adhesion of human monocytes and the monocytic cell line U937.

Abstract

Hypercholesterolemia is a major risk factor for development of atherosclerosis. In experimental animals fed a high-cholesterol diet, monocytes adhere to the arterial endothelium and penetrate into the intima where they differentiate into macrophages and ingest lipids thus giving rise to fatty streaks, the earliest type of atherosclerotic plaque. Macrophages express few receptors for normal low density lipoprotein (LDL) but can take up oxidized LDL by way of a scavenger receptor. The present study was designed to investigate the possible role of oxidized LDL in recruitment of resident intimal macrophages. We found that oxidized LDL induced enhanced expression of major histocompatibility complex class II molecules on human monocytes and U937 cells, a well-established system for studies of monocytic differentiation. Oxidized LDL also induced enhanced expression of the surface antigen LeuM3 but caused decreased expression of CD4 antigen, a pattern compatible with expression of a more-differentiated macrophage-like phenotype. Oxidized LDL also initiated aggregation of monocytes and U937 cells and stimulated adhesion of U937 cells to cultured endothelial cells. The results indicate that oxidized LDL may contribute to development of atherosclerosis by inducing adhesion of monocytes to the arterial intima and by stimulating intimal monocytes to differentiate into resident macrophages.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Holmes DR, Jr, Elveback LR, Frye RL, Kottke BA, Ellefson RD. Association of risk factor variables and coronary artery disease documented with angiography. Circulation. 1981 Feb;63(2):293–299. [PubMed]
  • Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease, and death. The Framingham study. Arch Intern Med. 1981 Aug;141(9):1128–1131. [PubMed]
  • Gerrity RG. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981 May;103(2):181–190. [PMC free article] [PubMed]
  • Joris I, Zand T, Nunnari JJ, Krolikowski FJ, Majno G. Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol. 1983 Dec;113(3):341–358. [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]
  • Gerrity RG, Goss JA, Soby L. Control of monocyte recruitment by chemotactic factor(s) in lesion-prone areas of swine aorta. Arteriosclerosis. 1985 Jan-Feb;5(1):55–66. [PubMed]
  • Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. [PubMed]
  • Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. [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]
  • 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]
  • Haberland ME, Fong D, Cheng L. Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits. Science. 1988 Jul 8;241(4862):215–218. [PubMed]
  • Gidlund M, Orn A, Pattengale PK, Jansson M, Wigzell H, Nilsson K. Natural killer cells kill tumour cells at a given stage of differentiation. Nature. 1981 Aug 27;292(5826):848–850. [PubMed]
  • Larsson LG, Ivhed I, Gidlund M, Pettersson U, Vennström B, Nilsson K. Phorbol ester-induced terminal differentiation is inhibited in human U-937 monoblastic cells expressing a v-myc oncogene. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2638–2642. [PMC free article] [PubMed]
  • Gidlund M, Rossi P, Cotran P, Ramstedt U, Wigzell H. In human monocytes a strong correlation exists between expression of the M3 antigen, Fc-mediated phagocytic activity and failure to participate in extracellular antibody-dependent cytotoxicity. Eur J Immunol. 1988 Mar;18(3):477–480. [PubMed]
  • Sundström C, Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. [PubMed]
  • Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. [PMC free article] [PubMed]
  • HAVEL RJ, EDER HA, BRAGDON JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. [PMC free article] [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • MCFARLANE AS. Labelling of plasma proteins with radioactive iodine. Biochem J. 1956 Jan;62(1):135–143. [PMC free article] [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]
  • Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med. 1976 Apr;15(2):212–216. [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]
  • Ralph P, Williams N, Moore MA, Litcofsky PB. Induction of antibody-dependent and nonspecific tumor killing in human monocytic leukemia cells by nonlymphocyte factors and phorbol ester. Cell Immunol. 1982 Aug;71(2):215–223. [PubMed]
  • Stewart SJ, Fujimoto J, Levy R. Human T lymphocytes and monocytes bear the same Leu-3(T4) antigen. J Immunol. 1986 May 15;136(10):3773–3778. [PubMed]
  • Moscicki RA, Amento EP, Krane SM, Kurnick JT, Colvin RB. Modulation of surface antigens of a human monocyte cell line, U937, during incubation with T lymphocyte-conditioned medium: detection of T4 antigen and its presence on normal blood monocytes. J Immunol. 1983 Aug;131(2):743–748. [PubMed]
  • Acres RB, Conlon PJ, Mochizuki DY, Gallis B. Rapid phosphorylation and modulation of the T4 antigen on cloned helper T cells induced by phorbol myristate acetate or antigen. J Biol Chem. 1986 Dec 5;261(34):16210–16214. [PubMed]
  • Adams DO, Hamilton TA. Molecular transductional mechanisms by which IFN gamma and other signals regulate macrophage development. Immunol Rev. 1987 Jun;97:5–27. [PubMed]
  • Quinn MT, Parthasarathy S, Steinberg D. Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5949–5953. [PMC free article] [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]
  • Henriksen T, Mahoney EM, Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6499–6503. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...