DIFFERENTIAL-EFFECTS OF UNSATURATED FATTY-ACIDS ON PHOSPHOLIPID-SYNTHESIS IN HUMAN LEUKEMIA MONOCYTIC U937 CELLS

The biosynthesis of phosphatidylcholine (PC), and phosphatidylethanolamine (PE) in monocyte-like leukemia U937 cells was monitored by adding [H-3]choline, [C-14]ethanolamine or [C-14]glycerol to the culture media; incorporation into phospholipid (PL) increased with time. The effect of unsaturated fatty acids (UFA) on PC and PE synthesis was investigated by pretreating U937 cells for 72 h with 10 mum 18: 1 (n - 9), 18: 2 (n - 6), 18: 3 (n - 3), 20: 4 (n - 6) and 20: 5 (n - 3). The UFA caused no alteration in cell growth, as evidenced by light microscopy and the incorporation of [H-3]thymidine and [H-3]leucine. Total cellular uptake of radioactive precursors remained unaffected by all the treatments. Pretreatment with 20:5 resulted in approximately 25 per cent reduction in the incorporation of [H-3]choline into PL, while no significant effect was detected with the other UFAs. 18:3, 20:4 and 20:5 depressed the incorporation of [C-14]ethanolamine into PL by 34 per cent, 28 per cent and 49 per cent respectively. However, there was no redistribution of label with any of the treatments. 18:3, 20:4 and 20:5 also antagonized the stimulatory effect of endotoxin (LPS) on PC and PE synthesis. In addition, the incorporation from [C-14]glycerol into PC and PE was reduced by 18:3, 20:4 and 20:5. Although the PL composition of the cells remained essentially unaffected, our study shows that chronic treatment of U937 cells with n - 3 PUFA (20:5) depressed PC and PE synthesis, and 18:3 and 20:4 also caused inhibition of PE synthesis.