Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein
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 /sup 125/I-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 /sup 14/C 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.
- Research Organization:
- Wihuri Research Institute, Helsinki, Finland
- OSTI ID:
- 5903667
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARTERIOSCLEROSIS
PATHOGENESIS
CARBON 14 COMPOUNDS
BIOSYNTHESIS
CHOLESTEROL
LABELLED COMPOUNDS
UPTAKE
LIPOPROTEINS
IN VITRO
IODINE 125
MACROPHAGES
MAST CELLS
OLEIC ACID
PHAGOCYTOSIS
SODIUM IODIDES
SULFATES
SULFUR 35
ALKALI METAL COMPOUNDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
HALIDES
HALOGEN COMPOUNDS
HYDROXY COMPOUNDS
INORGANIC PHOSPHORS
INTERMEDIATE MASS NUCLEI
IODIDES
IODINE COMPOUNDS
IODINE ISOTOPES
ISOTOPES
LIGHT NUCLEI
LIPIDS
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHAGOCYTES
PHOSPHORS
PROTEINS
RADIOISOTOPES
SODIUM COMPOUNDS
SOMATIC CELLS
STEROIDS
STEROLS
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
VASCULAR DISEASES
550201* - Biochemistry- Tracer Techniques