Unmodified low density lipoprotein causes cholesteryl ester accumulation in J774 macrophages

Area of Science:

• Cell Biology
• Atherosclerosis Research
• Lipid Metabolism

Background:

• Cholesteryl ester (CE)-loaded macrophages (foam cells) are key in atherosclerotic plaques.
• Typically, human monocytes/macrophages need chemically modified low-density lipoprotein (LDL) to accumulate CE.

Purpose of the Study:

• To investigate CE accumulation in J774 macrophages incubated with unmodified LDL.
• To elucidate the mechanisms of LDL uptake and CE storage in these cells.

Main Methods:

• Incubation of J774 macrophages with unmodified LDL.
• Analysis of CE content and localization (oil red O, electron microscopy).
• Fatty acid analysis of CE, receptor binding studies (125I-LDL), and assessment of receptor regulation (HMG-CoA reductase activity).

Main Results:

• J774 cells accumulated significant CE from unmodified LDL, forming foam cell-like inclusions.
• Cellular CE fatty acid composition differed from LDL-CE, indicating hydrolysis and reesterification.
• LDL uptake involved a receptor similar to the apolipoprotein B/E (apo B/E) receptor, with relative resistance to down-regulation.
• CE accumulation also occurred via non-specific internalization pathways.

Conclusions:

• J774 macrophage-like cells accumulate CE from unmodified LDL through both receptor-mediated and non-specific mechanisms.
• These findings highlight distinct pathways for foam cell formation compared to previously studied monocytes/macrophages.
• The relative resistance to down-regulation contributes to significant CE storage in J774 cells.