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An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Resveratrol and ω-3 PUFAs Promote Human Macrophage Differentiation and Function
Joseph Schwager1, Albine Bompard2, Daniel Raederstorff1
1DSM, HNC, Innovation, Global R&D Center, Wurmisweg 567, CH-4303 Kaiseraugst, Switzerland.
Abstract:
Monocytes differentiate into M1 and M2 macrophages, which are classically activated by microbial products such as LPS or IFN-γ and interleukins (e.g., the anti-inflammatory and Th2 promoting IL-4), respectively. The contribution of nutrients or nutrient-based substances such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and resveratrol (Res) on the differentiation and function of M1 and M2 macrophages was evaluated. THP-1 cells and peripheral blood mononuclear cells (PBMCs) were differentiated into M1 and M2 cells and activated with LPS/IFN-γ or IL-4/IL-13. Macrophage lineage specific surface determinants (e.g., CD11b, CD11c, CD14, CD206, CD209, CD274, HLA-DR, CCR7, CCR2) were analysed by cytofluorometry. Res and ω-3 PUFAs altered CD14, CD206, CD274 and HL-DR surface expression patterns in M1 and M2 macrophages differentiated from PBMC. LPS/IFN-γ or IL-14/IL-13 activated macrophages subpopulations, which secreted cytokines and chemokines as measured by multiplex ELISA. Res and ω-3 PUFA reduced IL-1β, IL-6, TNF-α, CXCL10/IP-10, CCL13/MCP-4 and CCL20/MIP-3α in LPS/IFN-γ activated human leukaemia THP-1 cells, which is indicative of a dampening effect on M1 macrophages. However, Res increased M1 prototypic cytokines such as IL-1β or IL-6 in macrophages derived from PBMCs and also modified the expression of IL-12p70. Collectively, Res and ω-3 PUFAs distinctly promoted the differentiation and function of M1 and M2 macrophages. We conclude that these substances strengthen the macrophage-mediated effects on the innate and adaptive immune response.
Insights
Nutrients like resveratrol and omega-3 PUFAs distinctly influence M1 and M2 macrophage differentiation and function, enhancing immune responses. These substances modulate macrophage polarization and cytokine secretion, impacting innate and adaptive immunity.
Area of Science:
- Immunology
- Cell Biology
- Nutritional Science
Background:
- Monocytes differentiate into M1 (classically activated) and M2 (alternatively activated) macrophages.
- M1 macrophages are activated by microbial products (LPS, IFN-γ), while M2 macrophages are activated by interleukins (IL-4).
- Nutrient-based substances like ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and resveratrol (Res) may influence macrophage polarization.
Purpose of the Study:
- To evaluate the contribution of ω-3 PUFAs and Res on the differentiation and function of M1 and M2 macrophages.
- To analyze the impact of these nutrients on macrophage surface marker expression and cytokine secretion.
- To understand how these substances modulate innate and adaptive immune responses via macrophage activation.
Main Methods:
- Differentiated THP-1 cells and peripheral blood mononuclear cells (PBMCs) into M1 and M2 macrophages.
- Activated macrophages using LPS/IFN-γ (M1) or IL-4/IL-13 (M2).
- Analyzed macrophage surface determinants by cytofluorometry and measured cytokine/chemokine secretion using multiplex ELISA.
Main Results:
- Resveratrol and ω-3 PUFAs altered surface marker expression (CD14, CD206, CD274, HLA-DR) in M1 and M2 macrophages derived from PBMCs.
- These nutrients reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in LPS/IFN-γ activated THP-1 cells, indicating a dampening effect on M1 macrophages.
- Resveratrol increased M1-associated cytokines (IL-1β, IL-6) in PBMC-derived macrophages and modified IL-12p70 expression.
Conclusions:
- Resveratrol and ω-3 PUFAs distinctly promote M1 and M2 macrophage differentiation and function.
- These nutrients modulate macrophage polarization and cytokine profiles, influencing immune cell activity.
- The findings suggest that Res and ω-3 PUFAs can strengthen macrophage-mediated innate and adaptive immune responses.
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