The binding and uptake of chylomicron remnants by human macrophages was studied in order to resolve paradoxical observations that have described the putative mechanisms by which postprandial lipoproteins induce foam cell formation. Chylomicron remnants bound to human monocyte-derived macrophages (HMMs) and to the transformed monocytic cell line THP-1 with high affinity (Kd of approx. 5.5 µg of chylomicron remnant protein/ml). Binding was found to be saturable for both cell types, and was strongly inhibited in the presence of unlabelled chylomicron remnants. Ligand blot studies with colloidal-gold-labelled chylomicron remnants identified two cell surface binding sites on both HMMs and THP-1 cells, with molecular masses of approx. 128 kDa and 43 kDa. The high-molecular-mass binding site was found to be the low-density lipoprotein (LDL) receptor, based on the strong inhibition of chylomicron remnant binding in the presence of unlabelled LDL, Fab2 antibody fragments to the LDL receptor or calcium chelators. Competition studies suggested that, in HMMs, the LDL receptor appeared to facilitate approximately half of the total chylomicron remnant uptake. In contrast, the LDL receptor was not significantly involved in macrophage uptake of chylomicron remnants by THP-1 cells. The identity of the 43 kDa binding site is presently unknown, but, importantly, expression was not inhibited as a consequence of sterol loading, which was induced by incubating HMMs and THP-1 cells with 25-hydroxycholesterol. In contrast, the expression of the LDL receptor was substantially attenuated following lipid loading. Collectively, our data suggest that, while the macrophage LDL receptor can bind chylomicron remnants and facilitate uptake in non-lipid-loaded HMMs, other sterol-insensitive sites are responsible for the unabated uptake of chylomicron remnants by macrophages. We propose that the 43 kDa macrophage chylomicron remnant binding protein may be a candidate for the sterol loading of macrophages.
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June 18 2001
Binding and uptake of chylomicron remnants by primary and THP-1 human monocyte-derived macrophages: determination of binding proteins
Caryn L. ELSEGOOD;
Caryn L. ELSEGOOD
1
*Department of Physiology, The University of Western Australia, Perth, Western Australia 6907, Australia
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Sebely PAL;
Sebely PAL
†Department of Nutrition, Dietetics and Food Sciences, Curtin University of Technology, Perth, Western Australia 6120, Australia
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Paul D. ROACH;
Paul D. ROACH
‡CSIRO (Australia) Division of Human Nutrition, Adelaide, South Australia 5000, Australia
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John C. L. MAMO
John C. L. MAMO
†Department of Nutrition, Dietetics and Food Sciences, Curtin University of Technology, Perth, Western Australia 6120, Australia
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Publisher: Portland Press Ltd
Received:
February 19 2001
Accepted:
March 31 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 101 (2): 111–119.
Article history
Received:
February 19 2001
Accepted:
March 31 2001
Citation
Caryn L. ELSEGOOD, Sebely PAL, Paul D. ROACH, John C. L. MAMO; Binding and uptake of chylomicron remnants by primary and THP-1 human monocyte-derived macrophages: determination of binding proteins. Clin Sci (Lond) 1 August 2001; 101 (2): 111–119. doi: https://doi.org/10.1042/cs1010111
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