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Updated: Jun 10, 2026
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is
Joshua J Anzinger1, Janet Chang, Qing Xu
1Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1422, USA.
Objective:
To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques).
Methods And Results:
We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis.
Conclusions:
Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells.
Insights
Human macrophages internalize native low-density lipoprotein (LDL) through two pinocytotic pathways: macropinocytosis and micropinocytosis. Both pathways are crucial for LDL uptake in macrophages within atherosclerotic plaques.
Area of Science:
- Cell Biology
- Cardiovascular Research
- Molecular Medicine
Background:
- Macrophages are key players in atherosclerosis.
- Macrophage uptake of low-density lipoprotein (LDL) contributes to plaque development.
- Understanding LDL uptake mechanisms is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the pinocytotic pathways involved in native LDL uptake by human macrophages.
- To identify specific mechanisms of LDL internalization in macrophages.
Main Methods:
- Utilized kinase and Rho GTPase inhibitors (SU6656, Toxin B) to study pinocytosis.
- Employed time-lapse microscopy to assess macropinocytosis.
- Investigated micropinocytosis using bafilomycin A1.
- Analyzed fluid-phase uptake pathways in macrophages.
Main Results:
- SU6656 and Toxin B partially inhibited LDL uptake by targeting macropinocytosis.
- Bafilomycin A1 partially inhibited LDL uptake by targeting micropinocytosis.
- Combined inhibition of macropinocytosis and micropinocytosis resulted in significant LDL uptake reduction (80%).
Conclusions:
- Human macrophages internalize native LDL via both macropinocytosis and micropinocytosis.
- Both pinocytotic pathways play a significant role in macrophage LDL uptake.
- Findings highlight the dual mechanism of LDL internalization in atherosclerotic macrophages.
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