Stimulation of Mast Cells Leads to Cholesterol Accumulation in Macrophages in vitro by a Mast Cell Granule-Mediated Uptake of Low Density Lipoprotein

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 8; pp. 2287 - 2291
• Main Authors: Kokkonen, Jorma O., Kovanen, Petri T.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.04.1987; National Acad Sciences
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Bacteriophages; Biological and medical sciences; Cells, Cultured; Cholesterol - metabolism; Cholesterol esters; Cholesterol Esters - metabolism; Cholesterols; Cytoplasmic Granules - metabolism; Fundamental and applied biological sciences. Psychology; Heparin; Histamines; Humans; Kinetics; lipoprotein (low density); Lipoproteins; Lipoproteins, LDL - metabolism; Lipoproteins, myelin; Macrophages; Macrophages - metabolism; Mast cells; Mast Cells - physiology; Mice; Oleic Acid; Oleic Acids - metabolism; Phagocytosis; Protamines; Proteins; Rats; Receptors, LDL - metabolism; Cell culture; Vertebrata; Mammalia; Mouse; Animal; Rodentia; β-Lipoprotein; Mast cell; Secretion granule; Accumulation; Cholesterol; Macrophage
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.8.2287

The uptake of low density lipoprotein (LDL) by cultured mouse macrophages was markedly promoted by isolated rat mast cell granules present in the culture medium. The granule-mediated uptake of LDL enhanced the rate of cholesteryl ester synthesis in the macrophages, the result being accumulation of cholesteryl esters in these cells. Binding of LDL to the granules was essential for the granule-mediated uptake of LDL by macrophages, for the uptake process was prevented by treating the granules with avidin or protamine chloride or by treating LDL with 1,2-cyclohexanedione, all of which inhibit the binding of LDL to the granules. Inhibition of granule phagocytosis by the macrophages with cytochalasin B also abolished the granule-mediated uptake of LDL. Finally, mouse macrophage monolayers and LDL were incubated in the presence of isolated rat serosal mast cells. Stimulation of the mast cells with compound 48/80, a degranulating agent, resulted in dose-dependent release of secretory granules from the mast cells and a parallel increase in cholesteryl ester synthesis in the macrophages. The results show that, in this in vitro model, the sequence of events leading to accumulation of cholesteryl esters in macrophages involves initial stimulation of mast cells, subsequent release of their secretory granules, binding of LDL to the exocytosed granules, and, finally, phagocytosis of the LDL-containing granules by macrophages.