Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum

Abstract

A monoclonal antibody, ASH1a/256C (256C), which binds to atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbit (WHHL) aorta in vivo, recognizes complex structures of phosphatidylcholine mixed with neutral lipids. In the present study, a cell culture system is described in which foam cells express 256C-positive lipid droplets. J774.1 macrophages were incubated in the presence of a small volume of WHHL serum for 24 h to produce foam cells, which were then incubated without the WHHL serum for 3 days. Oil red O-positive lipid droplets appeared on day 1, and were present in the cells during the whole incubation period. The lipid droplets in the cells were positively immunostained with antibody 256C on day 4, although they were negative on day 1. Expression of the antigenic lipid droplets was also induced by the addition of acetylated LDL or sera from patients with hyperlipidemia. When foam cells were induced by the addition of WHHL serum, cellular content of cholesteryl ester was greatly increased but then decreased to near basal levels by day 4. Concomitantly, cellular free cholesterol increased during the culture period, indicating that the cholesteryl ester changes to free cholesterol by day 4. The lipid droplets in the foam cells on day 4 were positively stained with filipin, a fluorescent probe for free cholesterol, as well as with 256C antibody, indicating that free cholesterol is enriched in antigenic lipid droplets. These observations suggest that hydrolysis and rearrangement of cellular cholesterol take place in foam cells to form complex structures of phosphatidylcholine and free cholesterol in lipid droplets. -

Lipid Droplets, the Central Hub Integrating Cell Metabolism and the Immune System

“…C. pneumonia infection results in the chronic inflammatory disease atherosclerosis, leading to lipid droplet-containing foam cell formation within arteries of the host ( Libbing et al, 2019 ). A previous study demonstrated that LDs can be enriched with free cholesterol from hyperlipidaemic serum due to hydrolysis and rearrangement of cellular cholesterol in foam cells ( Mori et al, 2001 ).…”

The Lipid-Droplet Proteome Reveals that Droplets Are a Protein-Storage Depot

“…Among organelles, the structure of lipid droplets is unique: A core of neutral lipid (triglycerides and sterol esters) is surrounded by a surface monolayer of polar lipids (cholesterol, phospholipids, and fatty acids) [2]. Abnormalities in intracellular lipid storage are associated with obesity and fatty liver, cardiovascular disease [3], diabetes [4], neutral lipid-storage disease [5], and Niemann Pick C disease [6].…”

Mycobacterium tuberculosis Infection-Driven Foamy Macrophages and Their Implications in Tuberculosis Control as Targets for Host-Directed Therapy

“…Alterations of metabolic pathways are involved not only in the inflammatory responses of macrophages but also in the transformation of Mtb-infected macrophages into foamy macrophages, which are the major contributors to TB pathogenesis (Figure 1B), as previously described (5, 6). Foamy macrophages are named based on their morphology as they contain bubble-like lipid bodies in their cytoplasm (53). Mtbinfected foamy macrophages have different features compared to non-foamy macrophages (Table 1, upper).…”