Related Experiment Videos
Distinct scavenger receptor expression and function in the human CD14(+)/CD16(+) monocyte subset
G Draude1, P von Hundelshausen, M Frankenberger
1Institut für Prophylaxe der Kreislaufkrankheiten, Klinikum Innenstadt, Ludwig-Maximilians-Universität, D-80336 Munich, Germany.
Abstract:
The CD14(+)/CD16(+) subset of human blood monocytes, which expresses low levels of the lipopolysaccharide receptor CD14 and high levels of the Fc receptor CD16 and exhibits features of mature tissue macrophages, is expanded in certain inflammatory conditions and may be relevant in atherosclerosis. Scavenger receptors (ScR) are important for lipid accumulation into macrophage-derived foam cells in atherogenesis and for the clearance of pathogens. Hence, we compared the function and expression of ScR in CD33(low) CD16(+) and CD33(high) CD14(++) monocyte subsets. Double immunofluorescence analysis of isolated monocytes revealed that the CD33(low) subset showed lower specific, ScR-mediated binding of DiI-labeled modified low-density lipoproteins (LDL) than CD33(high) cells. Differences in modified LDL binding between subsets were accompanied by changes in mRNA expression. RT-PCR in sorted cells indicated lower ScR class A type I/II (ScR-AI/II) mRNA levels in CD14(+)/CD16(+) than in CD14(++) cells, whereas CD36 transcripts were unaltered. This was paralleled by findings in mostly CD16(+) monocyte-derived macrophages showing a marked reduction in ScR-mediated binding of acetylated LDL, but not in the binding of oxidized LDL, and lower expression of ScR-AI/II mRNA, but not CD36 transcripts, after exposure to tumor necrosis factor-alpha for 48 h in vitro. Thus the subset of CD14(+)/CD16(+) monocytes shows distinct ScR function and expression, possibly reflecting a preactivation by cytokines with a predilection for specific inflammatory or vascular conditions, e.g., atherogenesis.
Insights
The CD14(+)/CD16(+) monocyte subset exhibits reduced scavenger receptor (ScR) function and expression, potentially impacting lipid accumulation in inflammatory conditions like atherosclerosis.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- The CD14(+)/CD16(+) monocyte subset displays characteristics of mature macrophages and is implicated in inflammatory diseases and atherosclerosis.
- Scavenger receptors (ScR) are crucial for lipid uptake in foam cells during atherogenesis and pathogen clearance.
Purpose of the Study:
- To compare scavenger receptor (ScR) function and expression between CD33(low) CD16(+) and CD33(high) CD14(++) monocyte subsets.
- To investigate the role of these monocyte subsets in the context of atherogenesis and inflammatory conditions.
Main Methods:
- Double immunofluorescence analysis of isolated human blood monocytes.
- Scavenger receptor-mediated binding assays using DiI-labeled modified low-density lipoproteins (LDL).
- Reverse transcription-polymerase chain reaction (RT-PCR) to quantify scavenger receptor mRNA expression (ScR-AI/II and CD36).
Main Results:
- The CD33(low) CD14(+)/CD16(+) monocyte subset demonstrated significantly lower ScR-mediated binding of modified LDL compared to the CD33(high) CD14(++) subset.
- mRNA expression analysis revealed lower ScR class A type I/II (ScR-AI/II) levels in CD14(+)/CD16(+) monocytes, while CD36 transcripts remained unchanged.
- In vitro studies with CD16(+) monocyte-derived macrophages showed reduced ScR-mediated binding of acetylated LDL and lower ScR-AI/II mRNA expression after TNF-alpha exposure.
Conclusions:
- The CD14(+)/CD16(+) monocyte subset possesses distinct ScR function and expression profiles.
- These differences suggest a potential preactivation state in this monocyte subset, influencing their role in inflammatory and vascular diseases such as atherosclerosis.