Original Article

Lysosomal lipid accumulation from oxidized low density lipoprotein is correlated with hypertrophy of the Golgi apparatus and trans-Golgi network

Correspondence to: W. Gray Jerome.

Lipid accumulation within macrophages is a major sequelae of atherosclerosis. Much of this lipid accumulation occurs within large, swollen lysosomes. We analyzed lipid accumulation in cultured macrophages using oxidized or acetylated low density lipoprotein (LDL) as the loading agent. Pigeon macrophages incubated for 48 h with mildly oxidized pigeon LDL (TBARS = 5–10 nmol/mg protein) showed significant increases in cellular cholesterol compared with untreated controls. Forty-eight percent of the increased cholesterol occurred as unesterified cholesterol. Treated cells had lipid-swollen lysosomes similar to those of atherosclerotic foam cells. The increase in lysosomal lipid was accompanied (correlation coefficient of 0.96) by increases in acid phosphatase staining cisternae of the Golgi and trans-Golgi network (TGN). THP-1 macrophages incubated with oxidized LDL showed similar lysosomal loading and Golgi/TGN hypertrophy. In contrast, macrophages incubated with acetylated LDL accumulated significant amounts of cholesterol but the increase occurred as cholesteryl ester (81% in pigeons) within cytoplasmic droplets and there was no associated increase in acid phosphatase-containing cisternae of Golgi or TGN.

The correlation in both pigeon and THP-1 macrophages of oxidized LDL-induced lysosomal lipid accumulation and Golgi hypertrophy suggests a linkage of these two phenomena. This implicates intracellular membrane trafficking as a possible defect in foam cells of the atherosclerotic lesion.—Jerome, W. G., C. Cash, R. Webber, R. Horton, and P. G. Yancey. Lysosomal lipid accumulation from oxidizied low density lipoprotein is correlated with hypertrophy of the Golgi apparatus and trans-Golgi network. J. Lipid Res. 1998. 39: 1362–1371.

Supplementary key words: atherosclerosis, macrophage, THP-1, pigeon, acetylated LDL

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. E. Cox, E. E. Griffin, J. C. Ullery, and W. G. Jerome Effects of cellular cholesterol loading on macrophage foam cell lysosome acidification J. Lipid Res., May 1, 2007; 48(5): 1012 - 1021. [Abstract] [Full Text] [PDF]

				E. E. Griffin, J. C. Ullery, B. E. Cox, and W. G. Jerome Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells J. Lipid Res., October 1, 2005; 46(10): 2052 - 2060. [Abstract] [Full Text] [PDF]

				Y. Wang, A. B. Castoreno, W. Stockinger, and A. Nohturfft Modulation of Endosomal Cholesteryl Ester Metabolism by Membrane Cholesterol J. Biol. Chem., March 25, 2005; 280(12): 11876 - 11886. [Abstract] [Full Text] [PDF]

				K. Hanasaki, K. Yamada, S. Yamamoto, Y. Ishimoto, A. Saiga, T. Ono, M. Ikeda, M. Notoya, S. Kamitani, and H. Arita Potent Modification of Low Density Lipoprotein by Group X Secretory Phospholipase A2 Is Linked to Macrophage Foam Cell Formation J. Biol. Chem., August 2, 2002; 277(32): 29116 - 29124. [Abstract] [Full Text] [PDF]

				P. G. Yancey and W. G. Jerome Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux J. Lipid Res., March 1, 2001; 42(3): 317 - 327. [Abstract] [Full Text]

				B. S. Dhaliwal and U. P. Steinbrecher Cholesterol delivered to macrophages by oxidized low density lipoprotein is sequestered in lysosomes and fails to efflux normally J. Lipid Res., October 1, 2000; 41(10): 1658 - 1665. [Abstract] [Full Text]

				N. L. Jones, J. W. Reagan, and M. C. Willingham The Pathogenesis of Foam Cell Formation : Modified LDL Stimulates Uptake of Co-Incubated LDL Via Macropinocytosis Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 773 - 781. [Abstract] [Full Text] [PDF]

				M. Lougheed, E. D. W. Moore, D. R. L. Scriven, and U. P. Steinbrecher Uptake of Oxidized LDL by Macrophages Differs From That of Acetyl LDL and Leads to Expansion of an Acidic Endolysosomal Compartment Arterioscler. Thromb. Vasc. Biol., August 1, 1999; 19(8): 1881 - 1890. [Abstract] [Full Text] [PDF]

				Y. Huang, A. Jaffa, S. Koskinen, A. Takei, and M. F. Lopes-Virella Oxidized LDL-Containing Immune Complexes Induce Fc Gamma Receptor I–Mediated Mitogen-Activated Protein Kinase Activation in THP-1 Macrophages Arterioscler. Thromb. Vasc. Biol., July 1, 1999; 19(7): 1600 - 1607. [Abstract] [Full Text] [PDF]