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Updated: Mar 23, 2026
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical
Rafaela F da Silva1, Jani Lappalainen2, Miriam Lee-Rueckert2
1Wihuri Research Institute, Helsinki, Finland; Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Background:
In atherosclerotic lesions, cholesterol-laden macrophage foam cells are formed and exposed to M1- and M2-polarizing factors. However, the effects of the polarizing factors on the proinflammatory and the anti-inflammatory potential of foam cells are not known.
Objective:
To investigate the effects of M1- and M2-polarizing factors on the expression of pro- and anti-inflammatory genes in cultured human macrophage foam cells.
Methods And Results:
Human monocytes were differentiated into macrophages in the presence of M-CSF, and then converted into cholesterol-loaded foam cells by incubation with acetylated LDL. The generated macrophages and foam cells were polarized into the M1 phenotype by classical activation with LPS and IFN-γ, or into the M2 phenotype by alternative activation with IL-4. When subjected to the M1-polarizing factors, the macrophages responded by typical upregulation of several key proinflammatory genes (TNFA, IL1B, CXCL8, CCL19, and COX2), while the anti-inflammatory genes (MRC1, CCL17, and IL10) displayed variable responses. The foam cells, again, showed a weaker response to the M1-polarizing factors, as indicated by reduced upregulation of the proinflammatory genes, reduced secretion of TNF-α, and a trend towards lower NF-κB activity. When subjected to alternative M2 polarization, both macrophages and foam cells responded by a typical upregulation of the anti-inflammatory genes, which was of equal magnitude in both cell types.
Conclusions:
Conversion of cultured human macrophages into foam cells suppresses their proinflammatory responses to M1-polarizing factors. Thus, in M1-polarizing microenvironments of atherosclerotic lesions, foam cell formation may locally weaken the macrophage-dependent inflammatory component of atherogenesis.
