Development of the Smooth Muscle Foam Cell: Uptake of Macrophage Lipid Inclusions

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 20; pp. 7760 - 7764
• Main Authors: Wolfbauer, Gertrud, Glick, Jane M., Minor, Lisa K., Rothblat, George H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.10.1986; National Acad Sciences
• Subjects: Ageing, cell death; Arteriosclerosis - pathology; Biological and medical sciences; Cell lines; Cell physiology; Cells, Cultured; Cholesterol esters; Cholesterol Esters - metabolism; Cholesterols; Cultured cells; Endocytosis; Foam cells; Fundamental and applied biological sciences. Psychology; Inclusion bodies; Inclusion Bodies - metabolism; Inclusions; Lipids; Macrophages; Macrophages - metabolism; Metabolic Clearance Rate; Molecular and cellular biology; Muscle, Smooth - metabolism; Muscle, Smooth - pathology; Phagocytosis; Smooth muscle myocytes; Vertebrata; Incorporation; Mammalia; Blood vessel; Atherosclerosis; Cell inclusion; Lipids; Smooth muscle; Mechanism; Macrophage; Myocyte
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.20.7760

A possible mechanism for the formation of smooth muscle foam cells in the atherosclerotic lesion was explored. Cultured macrophages (J774 cell line) were induced to form cytoplasmic cholesteryl ester inclusions by exposure to acetylated low density lipoprotein in the presence of cholesterol-rich phospholipid dispersions. The macrophages were disrupted by brief sonication, and the inclusions were isolated by flotation. When these inclusions were placed in direct contact with cultured smooth muscle cells, cellular uptake of the inclusions in a time- and dose-dependent manner was observed. Light and electron microscopy indicated the presence of lipid inclusions throughout the cytoplasm of the cells. Uptake of inclusion lipid by the smooth muscle cells was inhibited by several metabolic inhibitors, indicating that the process is dependent on metabolic activity. A modest but significant hydrolysis of the cholesteryl ester was observed, showing that the stored cholesteryl esters are metabolically available.