Modification of low density lipoproteins by secretory granules of rat serosal mast cells.
When low density lipoprotein (LDL) is incubated with granules isolated from rat serosal mast cells, a fraction of LDL is bound to the granule heparin proteoglycan. If incubation is continued at 37 degrees C, the bound LDL, but not the unbound LDL, is degraded by granule neutral proteases. In the early stage of incubation, all the granule-bound LDL can be released by 0.3 M NaCl (the "salt-sensitive" fraction of LDL). With time, an increasing proportion of the granule-bound LDL requires 0.5 M NaCl for release (the "salt-resistant" fraction of LDL). Chemical analysis showed that, on average, 20% of the apolipoprotein B LDL was lost from the salt-sensitive fraction and 60% from the salt-resistant fraction, without any change in the composition of the lipid portion. Electron microscopic analysis disclosed large fused particles of LDL (diameters up to 100 nm) in the highly proteolyzed salt-resistant fraction, but no fused particles could be found in the less proteolyzed salt-sensitive fraction. We conclude that both binding and extensive degradation of LDL by mast cell granules is required for fusion of LDL particles on the granule surface. As compared with native LDL, the mast cell granule-modified LDL particles exhibit (i) increased particle size, (ii) selective loss of protein (apoB), (iii) a decrease in hydrated density, and (iv) stronger ionic interaction between apoB and heparin proteoglycan. The particles resemble the extracellular lipid droplets found in atherosclerotic lesions of both man and animals. Modification of LDL by mast cells may therefore provide a model of how these lipid structures are formed.
Kovanen
P T
PT
Wihuri Research Institute, Helsinki, Finland.
Kokkonen
J O
JO
D000818:Animals; D002474:Cell-Free System; D002784:Cholesterol / Q000032:analysis; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010743:Phospholipids / Q000032:analysis; D011506:Proteins / Q000032:analysis; D051381:Rats; D012995:Solubility; D014280:Triglycerides / Q000032:analysis
D008077:Lipoproteins, LDL; D010743:Phospholipids; D011506:Proteins; D014280:Triglycerides; C032629:acetyl-LDL; D010664:Phenylmethylsulfonyl Fluoride; D002784:Cholesterol