Proteolytic enzymes of mast cell granules degrade low density lipoproteins and promote their granule-mediated uptake by macrophages in vitro.
Secretory granules exocytosed from rat serosal mast cells bind low density lipoprotein (LDL), and on being phagocytosed by macrophages, carry the bound LDL into these cells (Kokkonen, J. O., and Kovanen, P. T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 2287-2291). The binding of LDL to the granules is mediated through interactions between the apolipoprotein B (apoB) component of LDL and the heparin proteoglycan component of the granules. Here we report how degradation of apoB by the neutral proteases of the granules affects the granule-mediated uptake of LDL by cultured mouse macrophages. During incubation of LDL with proteolytically inactive granules, the rate of uptake of LDL by macrophages increased by 10-fold; whereas during incubation with proteolytically active granules, it increased by 50-fold, the increase in the rate of uptake during proteolysis correlating with the degree of apoB degradation. The 5-fold greater capacity of the proteolytically active granules to enhance the uptake of LDL resulted from their greater capacity to bind LDL, and consequently, to carry it into the macrophages. Electron microscopic analysis of LDL bound to the proteolytically active granules disclosed large spherical particles of fused LDL. The diameters of the granule-bound particles ranged up to 90 nm compared with an average diameter of 22 nm for both native LDL and the LDL bound to proteolytically inactive granules. The results show that granule proteases, by inducing fusion of granule-bound LDL, increase the amount of LDL bound per unit weight of granule heparin proteoglycan. Hence, the two components of mast cell granules, the proteases and the heparin proteoglycan, act in concert to promote the uptake of LDL by macrophages in vitro.
Kokkonen
J O
JO
Wihuri Research Institute, Helsinki, Finland.
Kovanen
P T
PT
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism* / Q000648:ultrastructure; D008407:Mast Cells / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010587:Phagocytosis; D013462:Sulfur Radioisotopes
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D013462:Sulfur Radioisotopes; D010447:Peptide Hydrolases