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Title: 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 secretorymore » granules, binding of LDL to the exocytosed granules, and, finally, phagocytosis of the LDL-containing granules by macrophages.« less
Authors:
;
Publication Date:
OSTI Identifier:
5903667
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States); Journal Volume: 84:8
Research Org:
Wihuri Research Institute, Helsinki, Finland
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 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