ALTERATIONS OF FATTY ACYL TURNOVER IN MACROPHAGE GLYCEROLIPIDS INDUCED BY STIMULATION - EVIDENCE FOR ENHANCED RECYCLING OF ARACHIDONIC-ACID

Glycerophospholipid biosynthesis by the de novo pathway was assessed i n mouse peritoneal macrophages by pulse-labeling with [U-C-14]glycerol . Phosphatidylcholine (PC), which amounts to about 35% of total cellul ar phospholipids, exhibited the highest rate of glycerol uptake, follo wed by phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Re modeling of PC molecular species by deacylation/reacylation was establ ished by determining the redistribution of glycerol label over 2 h aft er a 1 h pulse of [U-C-14]glycerol and by determining incorporation of O-18 from (H2O)-O-18-containing media. These data suggest that steari c and arachidonic acid enter PC primarily by the remodeling pathway bu t that small amounts of highly unsaturated molecular species, includin g 1,2-diarachidonoyl PC, are rapidly synthesized de novo, and subseque ntly remodeled or degraded. Treatment of the cells with the ionophore A23187 resulted in the selective enhancement of arachidonate turnover in PC, PI and neutral lipid, as well as enhanced de novo PI synthesis. [U-C-14]Glycerol labeling experiments suggest that arachidonic acid l iberated by Ca2+-dependent phospholipase A(2) activity is also reacyla ted in part through de novo glycerolipid biosynthesis, leading to the formation and remodeling of 1,2-diarachidonoyl PC and other highly pol yunsaturated molecular species.