Related Experiment Videos
Lipoproteins modulate expression of the macrophage scavenger receptor
1Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
Abstract:
Macrophage scavenger receptors (MSR) bind and internalize oxidized low density lipoprotein (OxLDL), a modified lipoprotein that is thought to be the proximal source of lipids that accumulate within cells of atherosclerotic lesions. The role of lipoproteins in modulating MSR expression are undetermined. We studied the effect of lipoproteins, native and modified LDL (acetylated LDL (AcLDL) and OxLDL) on the expression of the MSR in RAW cells, a murine macrophage cell line. Exposure to lipoproteins resulted in a marked induction of MSR mRNA expression (12- to 17-fold) with OxLDL and AcLDL having the greatest effects. Maximum induction occurred 1 hour after treatment with OxLDL and LDL. AcLDL induced a fourfold increase at 1 hour followed by a return to baseline and peak expression (sixfold) at 14 hours. Scavenger receptor function, as measured by 125I-AcLDL binding, was only modestly increased in response to lipoproteins. Incubation of macrophages with a cholesterol acceptor particle resulted in a dose-dependent decrease in MSR mRNA expression, which paralleled cholesterol loss from the cells. OxLDL did not affect MSR mRNA stability, implying that MSR mRNA was transcriptionally regulated by lipoproteins. Finally, peritoneal macrophages were isolated from mice following intraperitoneal injection of lipoproteins. Macrophage expression of MSR mRNA was significantly (16-fold) increased by LDL, AcLDL, or OxLDL relative to mice infused with phosphate-buffered saline. This demonstration that exposure to lipoproteins increases expression of the macrophage scavenger receptor implies that lipoproteins can further contribute to foam cell development in atherosclerosis.
Insights
Lipoproteins, including oxidized LDL (OxLDL), significantly increase macrophage scavenger receptor (MSR) mRNA expression. This suggests lipoproteins may worsen foam cell development in atherosclerosis.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Macrophage scavenger receptors (MSR) internalize oxidized low-density lipoprotein (OxLDL), a key lipid source in atherosclerotic lesions.
- The influence of lipoproteins on MSR expression remains unclear.
Purpose of the Study:
- To investigate the effect of native and modified LDL on MSR expression in macrophages.
- To determine the regulatory mechanisms of MSR expression by lipoproteins.
Main Methods:
- RAW cells and primary murine macrophages were treated with various LDL preparations (native, acetylated, oxidized).
- MSR mRNA expression was quantified using RT-PCR.
- Macrophage scavenger receptor function was assessed via 125I-AcLDL binding assays.
- MSR mRNA stability was evaluated.
- Peritoneal macrophages were isolated from lipoprotein-injected mice.
Main Results:
- Lipoprotein exposure, particularly OxLDL and acetylated LDL (AcLDL), markedly induced MSR mRNA expression (12- to 17-fold) in RAW cells.
- OxLDL and native LDL peaked MSR mRNA induction at 1 hour, while AcLDL showed a delayed secondary peak.
- Scavenger receptor function showed only modest increases.
- Cholesterol acceptor treatment decreased MSR mRNA expression, correlating with cholesterol loss.
- OxLDL did not affect MSR mRNA stability, indicating transcriptional regulation.
- In vivo, LDL, AcLDL, and OxLDL significantly increased MSR mRNA in peritoneal macrophages (16-fold).
Conclusions:
- Lipoproteins, including OxLDL and AcLDL, transcriptionally upregulate macrophage scavenger receptor (MSR) expression.
- Increased MSR expression by lipoproteins may contribute to lipid accumulation and foam cell formation in atherosclerosis.