Low density lipoprotein degradation by rat mast cells. Demonstration of extracellular proteolysis caused by mast cell granules.
The interaction between rat serosal mast cells and low density lipoproteins (LDL) was studied in vitro. When rat 125I-LDL was incubated with mast cells, it was bound to a binding site on the mast cell surface but was not internalized by the cells. Even though 125I-LDL was not internalized, its protein component, apolipoprotein B, was rapidly degraded. The proteolytic activity responsible for the degradation of apolipoprotein B was present in the extracellular fluid of mast cells. It could be shown that the degradation was caused entirely by specific cell organelles of mast cells, the granules, which were spontaneously released into the extracellular fluid during preparation and incubation of the cells. In contrast to uncontrolled spontaneous degranulation, a controlled specific degranulation of mast cells can be induced by treating the cells with the compound 48/80. When increasing amounts of 48/80 were added to mast cell suspensions, a dose-dependent release of granules was observed and an increase in the rate of 125I-LDL degradation resulted. The increase in 125I-LDL degradation closely followed the increase in granule release. Thus, a quantitative relationship between the amount of granules present in the extracellular fluid and the amount of degradation of 125I-LDL could be established. The apolipoprotein part of LDL was extensively degraded by isolated mast cell granules. Analysis by polyacrylamide gel electrophoresis showed that upon incubation of LDL with isolated granules, the apolipoprotein B band rapidly disappeared with simultaneous appearance of several low molecular weight bands. The degradation of 125I-LDL by mast cell granules proceeded optimally at neutral pH and at physiological ionic strength. The results show that mast cell granules are able to efficiently degrade LDL in vitro, once released from mast cells into the extracellular fluid.
D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats
D008077:Lipoproteins, LDL; D010447:Peptide Hydrolases