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Preferential uptake of cholesteryl ester-HDL by cultured macrophages
Abstract:
The interaction between HDL and macrophages in culture was studied using HDL labeled with 125I and with [3H]cholesteryl linoleyl ether. Mouse peritoneal macrophages and the macrophage-like cell lines J-774 and CT2, of mouse origin, took up and metabolized rat HDL and human HDL3. In all 3 cell types using both rat and human HDL, the uptake of the cholesteryl ester moiety as measured with the nondegradable cholesteryl ether analog, was 2-5-fold higher when compared to the protein moiety. Modulation of the cholesterol content of the cultured macrophages affected the uptake of both protein and lipid moieties of HDL to the same extent. When the macrophages had interacted with the labeled HDL for 5 h and were post-incubated for 20 h, the amount of [125I]HDL which reappeared in the post incubation medium was twice that of [3H]cholesteryl linoleyl ether-HDL. The site from which the HDL may have returned to the culture medium was tentatively localized to the trypsin-releasable, cell surface-related compartment. The present results indicate that interaction between macrophages and HDL may result in some loss of cholesteryl ester and possibly render the particle more receptive for cellular cholesterol removal.
Insights
Macrophages readily absorb cholesterol esters from high-density lipoprotein (HDL). This interaction may facilitate cholesterol removal from cells, impacting HDL particle composition.
Area of Science:
- Biochemistry
- Cell Biology
- Lipid Metabolism
Background:
- High-density lipoprotein (HDL) plays a crucial role in reverse cholesterol transport.
- Macrophages are key cells involved in cholesterol homeostasis and atherosclerosis.
Purpose of the Study:
- To investigate the interaction and metabolism of HDL by macrophages in vitro.
- To understand how macrophages uptake and process HDL components.
Main Methods:
- Utilized radiolabeled HDL (125I for protein, [3H]cholesteryl linoleyl ether for lipid).
- Employed mouse peritoneal macrophages and macrophage cell lines (J-774, CT2).
- Assessed uptake and metabolism of HDL components.
Main Results:
- Macrophages exhibited higher uptake of HDL cholesteryl ester moiety compared to the protein moiety (2-5 fold).
- Cellular cholesterol content modulated HDL uptake proportionally for both lipid and protein.
- Released HDL showed a higher proportion of protein than cholesteryl ester after incubation.
Conclusions:
- Macrophages actively internalize and metabolize HDL, preferentially taking up cholesteryl esters.
- HDL interaction with macrophages can lead to cholesteryl ester loss, potentially enhancing cholesterol efflux.
- A trypsin-releasable cell surface compartment may be involved in HDL release.