CHYMASE IN EXOCYTOSED RAT MAST-CELL GRANULES EFFECTIVELY PROTEOLYZES APOLIPOPROTEIN AL-CONTAINING LIPOPROTEINS, SO REDUCING THE CHOLESTEROLEFFLUX-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 lipoprotein(3) (HDL(3 )), and so reduces its ability to induce cholesterol efflux from macro phage 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 ef flux from cultured macrophage foam cells. Inhibition was strongest whe n remnants were added to apolipoprotein AI (apoAI)-containing lipoprot eins; the remnants had no effect on the weaker efflux produced by apoA I-deficient serum. Western blot analysis showed that granule remnants degrade apoAI in serum and in intimal fluid, When released from remnan ts, chymase lost its ability to proteolyze HDL(3) in the presence of s erum. Thus, remnant chymase (but not isolated chymase) was able to res ist the natural protease inhibitors present in serum and in intimal fl uid, The results imply participation of exocytosed mast cell granules in foam cell formation in atherognesis.