Acyl Chain Preference in Foam Cell Formation from Mouse Peritoneal Macrophages.

ABSTRACT

Macrophage foam cells play critical roles in the initiation and development of atherosclerosis by synthesizing and accumulating cholesteryl ester (CE) in lipid droplets. However, in analyzing lipid metabolism in foam cell formation, studies have focused on the sterol group, and little research has been done on the acyl chains. Therefore, we adapted a model system using liposomes containing particular acyl chains and examined the effect of various acyl chains on foam cell formation. Of the phosphatidylserine (PS) liposomes tested containing PS, phosphatidylcholine, and cholesterol, we found that unsaturated (C181), but not saturated (C160 and C180), PS liposomes induced lipid droplet formation, indicating that foam cell formation depends on the nature of the acyl chain of the PS liposomes. Experiments on the uptake and accumulation of cholesterol from liposomes by adding [14C]cholesterol suggested that foam cell formation could be induced only when cholesterol was converted to CE in the case of C181 PS liposomes. Both microscopic observations and metabolic analysis suggest that cholesterol incorporated into either C160 or C180 PS liposomes may stay intact after being taken in by endosomes. The [14C]C181 fatty acyl chain in the C181 PS liposome was used to synthesize CE and triacylglycerol (TG). Interestingly, the [14C]C160 in the C181 PS liposome was metabolized to sphingomyelin rather than being incorporated into either CE or TG, which could be because of enzymatic acyl chain selectivity. In conclusion, our results indicate that the acyl chain preference of macrophages could have some impact on their progression to foam cells.