Abstract
Mast cells and macrophages coexist in the human arterial intima where oxidation of low density lipoproteins (LDL) also takes place during atherosclerosis. To investigate whether mast cells play a role in macrophage-mediated oxidation of LDL, a model system was designed in which mast cells and macrophages were cocultured in incubation medium containing LDL. Stimulation of rat serosal mast cells to induce exocytosis of their cytoplasmic granules was found to inhibit macrophage-mediated oxidation of LDL. The inhibitory effect depended on the ability of mast cell-derived histamine, released from the exocytosed granules into the medium, to bind the copper ions necessary for propagation of the macrophage-initiated oxidation of LDL. In addition to binding free copper ions, the mast cell-derived histamine was also capable of inhibiting oxidation of LDL propagated by copper ions bound to the apolipoprotein B component of the LDL particle. The results indicate that mast cells may prevent cell-mediated oxidation of LDL and imply a potentially preventive role for the mast cell in atherosclerosis.
Highlights
The presence of mast cells has been demonstrated in the atherosclerotic intima of man and of several mammalian species (6, 7)
Critical for this low density lipoproteins (LDL) modification and uptake by macrophages was found to be the interaction of LDL with exocytosed granule remnants of the stimulated mast cells: first the apolipoprotein B of LDL binds to the heparin proteoglycan component of the granule remnant, and the insoluble neutral proteases chymase and carboxypeptidase A, which alsoremain in the granule remnant, degrade the apoB of LDL, whereupon the LDL particles on the granule remnant surface fuse
The present study demonstrates that one cell type present in the arterial intima, the mast cell, if stimulated to degranulate, is capable of inhibiting oxidation of LDL by another cell type present in intima, the macrophage
Summary
Materials and Animals-Compound 48/80, histamine, and bovine serum albumin were obtained from Sigma. Separation of Copper-chelating Compounds from the Ultrafiltrate on a Copper Zon-SephuroseColumn-Three-hundred pl of the ultrafiltrate (
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