Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL—CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway.
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August 2002
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Research Article|
August 15 2002
Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions
Tao FU;
Tao FU
Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, U.S.A.
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Jayme BORENSZTAJN
Jayme BORENSZTAJN
1
Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, U.S.A.
1To whom correspondence should be addressed (e-mail jbb@northwestern.edu).
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Publisher: Portland Press Ltd
Received:
January 09 2002
Revision Received:
April 24 2002
Accepted:
May 23 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (1): 195–201.
Article history
Received:
January 09 2002
Revision Received:
April 24 2002
Accepted:
May 23 2002
Citation
Tao FU, Jayme BORENSZTAJN; Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions. Biochem J 15 August 2002; 366 (1): 195–201. doi: https://doi.org/10.1042/bj20020045
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