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An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex
Rafael Nambo-Venegas1, Berenice Palacios-González2, Jaime Mas-Oliva3
1Laboratorio de Estructura de Proteínas, Instituto Nacional de Medicina Genómica, Mexico City 14600, Mexico.
Background:
M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related changes in the transcriptome of M1 macrophages during the internalization process of LDL particles.
Methods:
Peripheral blood mononuclear cells (PBMCs) from healthy male and female subjects were separated using Hystopaque, and monocytes were isolated from PBMCs using a positive selection of CD14+ cells. Cells were stimulated with LDL 10 µg/mL, and the transcriptional profile of M1 macrophages performed during LDL internalization was determined using a Clariom D platform array.
Results:
Chromosome Y influences the immune system and inflammatory responses in males expressing 43% of transcripts in response to LDL treatment. Males and females share 15 transcripts, where most correspond to non-coding elements involved in oxidative stress and endothelial damage.
Conclusions:
During LDL internalization, male monocyte-derived M1 macrophages display more marked proinflammatory gene expression. In contrast, female M1 macrophages display a more significant number of markers associated with cell damage.
Insights
Male M1 macrophages show heightened pro-inflammatory gene expression upon low-density lipoprotein (LDL) uptake. Female M1 macrophages exhibit more cell damage markers, indicating distinct sex-related responses in atherosclerosis.
Area of Science:
- Immunology
- Cardiovascular Biology
- Genomics
Background:
- M1 macrophages, crucial in inflammation, become foam cells when exposed to low-density lipoproteins (LDL).
- Atherosclerotic plaques show more advanced lesions and infiltration in males.
- Sex-based differences in macrophage responses to LDL are critical for understanding atherosclerosis.
Purpose of the Study:
- To investigate sex-specific transcriptomic changes in M1 macrophages during LDL internalization.
- To identify differential gene expression patterns between male and female M1 macrophages in response to LDL.
Main Methods:
- Isolation of monocytes from peripheral blood mononuclear cells (PBMCs) of healthy males and females.
- Stimulation of CD14+ cells with LDL (10 µg/mL) to induce M1 macrophage phenotype.
- Transcriptome analysis using Clariom D platform array during LDL internalization.
Main Results:
- Male M1 macrophages exhibited 43% of transcripts influenced by the Y chromosome in response to LDL.
- Shared transcripts between sexes primarily involved non-coding elements related to oxidative stress and endothelial damage.
- Significant differences in gene expression profiles were observed between male and female M1 macrophages.
Conclusions:
- Male monocyte-derived M1 macrophages demonstrate a more pronounced pro-inflammatory gene expression profile during LDL internalization.
- Female M1 macrophages present a greater number of markers associated with cellular damage.
- These findings highlight distinct sex-specific immune responses in the context of LDL-induced inflammation and atherosclerosis.
