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Updated: Jun 20, 2026
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Macropinocytosis contributes to the macrophage foam cell formation in RAW264.7 cells
1Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China.
Abstract:
The key event in the atherosclerosis development is the lipids uptake by macrophage and the formation of foam cell in subendothelial arterial space. Besides the uptake of modified low-density lipoprotein (LDL) by scavenger receptor-mediated endocytosis, macrophages possess constitutive macropinocytosis, which is capable of taking up a large quantity of solute. Macrophage foam cell formation could be induced in RAW264.7 cells by increasing the serum concentration in the culture medium. Foam cell formation induced by serum could be blocked by phosphoinositide 3-kinase inhibitor, LY294002 or wortmannin, which inhibited macropinocytosis but not receptor-mediated endocytosis. Further analysis indicated that macropinocytosis took place at the gangliosides-enriched membrane area. Cholesterol depletion by beta-methylcyclodextrin-blocked macropinocytosis without affecting scavenger receptor-mediated endocytosis of modified LDLs. These results suggested that macropinocytosis might be one of the important mechanisms for lipid uptake in macrophage. And it made significant contribution to the lipid accumulation and foam cell formation.
Insights
Macrophage macropinocytosis, a key lipid uptake pathway, significantly contributes to foam cell formation in atherosclerosis. Inhibiting macropinocytosis blocks lipid accumulation, suggesting its crucial role in disease development.
Area of Science:
- Cell biology
- Cardiovascular research
- Atherosclerosis pathogenesis
Background:
- Atherosclerosis involves lipid uptake by macrophages and foam cell formation.
- Macrophages utilize scavenger receptor-mediated endocytosis and macropinocytosis for solute uptake.
Purpose of the Study:
- To investigate the role of macrophage macropinocytosis in lipid uptake and foam cell formation.
- To determine if macropinocytosis contributes to lipid accumulation in macrophages.
Main Methods:
- Macrophage foam cell formation induced in RAW264.7 cells by increasing serum concentration.
- Inhibition of macropinocytosis using phosphoinositide 3-kinase inhibitors (LY294002, wortmannin).
- Assessment of lipid uptake via macropinocytosis and scavenger receptor-mediated endocytosis under cholesterol depletion (beta-methylcyclodextrin).
Main Results:
- Serum-induced foam cell formation was blocked by macropinocytosis inhibitors.
- Macropinocytosis occurs in ganglioside-enriched membrane areas.
- Cholesterol depletion inhibited macropinocytosis but not LDL uptake via scavenger receptors.
Conclusions:
- Macropinocytosis is a significant mechanism for lipid uptake in macrophages.
- Macropinocytosis contributes substantially to lipid accumulation and foam cell formation.
- Targeting macropinocytosis may offer a therapeutic strategy for atherosclerosis.
