FATTY-ACID METABOLISM IN HUMAN-LYMPHOCYTES .2. ACTIVATION OF FATTY-ACID DESATURASE-ELONGASE SYSTEMS DURING BLASTIC TRANSFORMATION

The fatty acid desaturation-elongation ability of human T-lymphocytes during blastic transformation was determined both by gas-liquid chromatography and incubation with radiolabeled precursors. Human peripheral blood mononuclear cells (PBMC) were activated with phytohemagglutinin (PHA) and cultured in media supplemented with different fatty acids (18:0, 18:1(n - 9), 18:2(n - 6), 18:3(n - 3) and 20:4(n - 6)) at a final concentration of 30 μM. All the fatty acids added were elongated by activated PBMC and the maximal activity was observed on 20:4(n - 6) (a 25% of conversion to 22:4(n - 6)). Supplementation with stearic acid increased the proportion of oleic (from 21.4% to 23.7%) and eicosaenoic (from 3.1% to 5.7%) acids in cellular lipids, indicating the existence of a Δ9-desaturase activity. Supplementation with linoleic and linolenic acids increased slightly the cell content in their more unsaturated derivatives. Direct measurement of desaturase activities was performed by incubating quiescent and activated PBMC with [1-14C]stearic, [1-14C]linoleic and [1-14C]linolenic acids. Quiescent cells exhibited a very low Δ9-desaturase and no sign of Δ6-desaturase activity. A moderate and progressive activation of Δ9-, Δ6- and Δ5-desaturases was observed during blastic transformation of human PBMC. Up to 8% of 18:0 was converted to monoenes, 4% and 1.5% of 18:2(n - 6) was converted to trienes and tetraenes, respectively, and 14.5% of 18:3(n - 3) was converted to pentaenes. The maximal relative activities were found after 48 h of PHA-stimulation for Δ9-desaturase (around 90 pmol of 18:0 converted per 106 cells in the last 24 h) and at 72 h for Δ6- and Δ5-desaturases (around 75 and 140 pmol of 18:2 and 18:3, respectively, converted per 107 cells in the last 24 h). Although these activities are not enough to explain all the changes in fatty acid composition of human PBMC during blastic transformation, they may contribute to a more controlled cell phospholipid composition. © 1990.