Chymase in exocytosed rat mast cell granules effectively proteolyzes apolipoprotein AI-containing lipoproteins, so reducing the cholesterol efflux-inducing ability of serum and aortic intimal fluid.
Degranulated mast cells are present in human fatty streaks. Chymase in granules released from degranulated rat serosal mast cells, i.e., in granule remnants, proteolyzes human high density lipoprotein3 (HDL3), and so reduces its ability to induce cholesterol efflux from macrophage foam cells in vitro. In this study we found that remnant chymase, by proteolyzing human serum and human aortic intimal fluid, prevents these two physiologic fluids from effectively inducing cholesterol efflux from cultured macrophage foam cells. Inhibition was strongest when remnants were added to apolipoprotein AI (apoAI)-containing lipoproteins; the remnants had no effect on the weaker efflux produced by apoAI-deficient serum. Western blot analysis showed that granule remnants degrade apoAI in serum and in internal fluid. When released from remnants, chymase lost its ability to proteolyze HDL3 in the presence of serum. Thus, remnant chymase (but not isolated chymase) was able to resist the natural protease inhibitors present in serum and in intimal fluid. The results imply participation of exocytosed mast cell granules in foam cell formation in atherogenesis.
Lindstedt
L
L
Wihuri Research Institute, Helsinki, Finland.
Lee
M
M
Castro
G R
GR
Fruchart
J C
JC
Kovanen
P T
PT
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology; D001790:Blood Physiological Phenomena; D002784:Cholesterol / Q000378:metabolism*; D053818:Chymases; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000502:physiology*
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol; D012697:Serine Endopeptidases; D053818:Chymases