Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species
Macrophage foam cells of atherosclerotic lesions store lipid in lysosomes and cytoplasmic inclusions. Oxidized low density lipoprotein (oxLDL) has been proposed to be the atherogenic particle responsible for the free and esterified cholesterol stores in macrophages. Currently, however, there is a pa...
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| Format: | Article |
| Language: | English |
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Elsevier
1998-07-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520325153 |
| _version_ | 1818727045092343808 |
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| author | Patricia G. Yancey W. Gray Jerome |
| author_facet | Patricia G. Yancey W. Gray Jerome |
| author_sort | Patricia G. Yancey |
| collection | DOAJ |
| description | Macrophage foam cells of atherosclerotic lesions store lipid in lysosomes and cytoplasmic inclusions. Oxidized low density lipoprotein (oxLDL) has been proposed to be the atherogenic particle responsible for the free and esterified cholesterol stores in macrophages. Currently, however, there is a paucity of data showing that oxLDL can induce much cholesterol accumulation in cells. The present studies compare the ability of mildly oxLDL (TBARS = 5 to 10 nmols/mg LDL protein) with acetylated LDL to induce free cholesterol (FC) and esterified cholesterol (EC) accumulation in pigeon, THP-1, and mouse macrophages. Mildly oxLDL stimulated high levels of loading comparable to acLDL where the cellular cholesterol concentrations ranged from 160 to 420 μg/mg cell protein with EC accounting for 52–80% of the cholesterol. Pigeon and THP-1 macrophages stored most (60–90%) of oxLDL cholesterol (both FC and EC) in lysosomes, and the bulk (64–88%) of acLDL cholesterol in cytoplasmic inclusions. Consistent with lysosomal accumulation, cholesterol esterification was 75% less in THP-1 macrophages enriched with oxLDL cholesterol compared with acLDL. Furthermore, addition of an acyl-CoA:cholesterol acyltransferase inhibitor did not significantly affect either cholesterol loading or the percent distribution of FC and EC in THP-1 and pigeon cells incubated with oxLDL. Surprisingly, mouse macrophages stored most of oxLDL (71%) and acLDL (83%) cholesterol within cytoplasmic inclusions. Also, in mouse macrophages, esterification paralleled cholesterol loading, and was 3-fold more in oxLDL treated cells compared with acLDL treated cells. Inhibition of ACAT led to a 62% and 90% reduction in the %EC in oxLDL and acLDL treated mouse macrophages, respectively. The results demonstrate that mildly oxidized low density lipoprotein (oxLDL) stimulates macrophage foam cell formation and lipid engorgement of lysosomes. However, the fate of oxLDL cholesterol markedly differs in macrophages of different species.—Yancey, P. G., and W. G. Jerome. Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species. J. Lipid Res. 1998. 39: 1349–1361. |
| first_indexed | 2024-12-17T22:07:51Z |
| format | Article |
| id | doaj.art-7204576fa0e84d28a0f9faf626f82fd3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:07:51Z |
| publishDate | 1998-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7204576fa0e84d28a0f9faf626f82fd32022-12-21T21:30:48ZengElsevierJournal of Lipid Research0022-22751998-07-0139713491361Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different speciesPatricia G. Yancey0W. Gray Jerome1Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1092To whom correspondence should be addressed.; Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1092Macrophage foam cells of atherosclerotic lesions store lipid in lysosomes and cytoplasmic inclusions. Oxidized low density lipoprotein (oxLDL) has been proposed to be the atherogenic particle responsible for the free and esterified cholesterol stores in macrophages. Currently, however, there is a paucity of data showing that oxLDL can induce much cholesterol accumulation in cells. The present studies compare the ability of mildly oxLDL (TBARS = 5 to 10 nmols/mg LDL protein) with acetylated LDL to induce free cholesterol (FC) and esterified cholesterol (EC) accumulation in pigeon, THP-1, and mouse macrophages. Mildly oxLDL stimulated high levels of loading comparable to acLDL where the cellular cholesterol concentrations ranged from 160 to 420 μg/mg cell protein with EC accounting for 52–80% of the cholesterol. Pigeon and THP-1 macrophages stored most (60–90%) of oxLDL cholesterol (both FC and EC) in lysosomes, and the bulk (64–88%) of acLDL cholesterol in cytoplasmic inclusions. Consistent with lysosomal accumulation, cholesterol esterification was 75% less in THP-1 macrophages enriched with oxLDL cholesterol compared with acLDL. Furthermore, addition of an acyl-CoA:cholesterol acyltransferase inhibitor did not significantly affect either cholesterol loading or the percent distribution of FC and EC in THP-1 and pigeon cells incubated with oxLDL. Surprisingly, mouse macrophages stored most of oxLDL (71%) and acLDL (83%) cholesterol within cytoplasmic inclusions. Also, in mouse macrophages, esterification paralleled cholesterol loading, and was 3-fold more in oxLDL treated cells compared with acLDL treated cells. Inhibition of ACAT led to a 62% and 90% reduction in the %EC in oxLDL and acLDL treated mouse macrophages, respectively. The results demonstrate that mildly oxidized low density lipoprotein (oxLDL) stimulates macrophage foam cell formation and lipid engorgement of lysosomes. However, the fate of oxLDL cholesterol markedly differs in macrophages of different species.—Yancey, P. G., and W. G. Jerome. Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species. J. Lipid Res. 1998. 39: 1349–1361.http://www.sciencedirect.com/science/article/pii/S0022227520325153mildly oxidized LDLmacrophage foam cellslipid-engorged lysosomes |
| spellingShingle | Patricia G. Yancey W. Gray Jerome Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species Journal of Lipid Research mildly oxidized LDL macrophage foam cells lipid-engorged lysosomes |
| title | Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species |
| title_full | Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species |
| title_fullStr | Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species |
| title_full_unstemmed | Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species |
| title_short | Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species |
| title_sort | lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species |
| topic | mildly oxidized LDL macrophage foam cells lipid-engorged lysosomes |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520325153 |
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