UTILIZATION OF GAMMA-LINOLENIC ACID BY MOUSE PERITONEAL-MACROPHAGES

To delineate the metabolism of gammalinolenic acid (18:3(n-6)) by macrophages, primary cultures of resident mouse peritoneal macrophages were incubated with [C-14]18:3(n-6). At 3, 6 or 20 h, the majority (> 85%) of the radiolabel was recovered in cell phospholipids. With increasing time of incubation, a relative reduction of C-14 in glycerophosphocholine (ChoGpl, 58.1% to 46.2%) was noted. This was offset by a corresponding increase in glycerophosphoethanolamine (EtnGpl) labeling (from 8.8% to 18.9%). There was also a time-dependent redistribution of C-14 from diacyl to ether-containing phospholipid subclasses in ChoGpl and EtnGpl. Analysis of cell extracts by reverse-phase HPLC following transmethylation demonstrated that 18:3(n-6) was extensively elongated (> 80%) to dihomogammalinolenic acid (20:3(n-6)) by 3 h. The major radiolabeled phospholipid molecular species in the diacyl (PtdCho) and alkylacylglycerophosphocholine (PakCho) subclasses was 16:0-20:3(n-6). In contrast, diacyl (PtdEtn) and alkenylacylglycerophosphoethanolamine (PlsEtn) subclasses contained primarily [C-14]18:0-20:3(n-6) and 16:0-20:3(n-6), respectively. Macrophages prelabeled with [C-14]18:3(n-6) for 20 h and stimulated with calcium ionophore A23187 or zymosan synthesized [C-14]prostaglandin E, (PGE1). These data demonstrate that macrophages possess an active long chain polyunsaturated fatty acid elongase capable of converting 18:3(n-6) to 20:3(n-6) which can, upon stimulation, be converted to PGE1.