Phospholipase D as a potential target for the antiproliferative effects of polyunsaturated fatty acids in rat thymocytes

The effects of various saturated and unsaturated fatty acids (FAs) on the proliferative response and phospholipase D (PLD) activity of rat thymocytes were investigated. When added to culture medium as complexes with albumin, all the FAs tested, except stearic acid, inhibited the ConA-induced thymocyte proliferation, eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids being the most inhibitory. Apart from 22:6n-3 which slightly increased the percentage of late apoptotic and necrotic thymocytes in the presence of mitogen, none of the FAs induced significant apoptosis or necrosis. A short 2-h preincubation of rat thymocytes in the presence of FA–albumin complexes was sufficient to induce a significant enrichment of cell phospholipids with each FA and to stimulate thymocyte PLD activity. However, 20:5n-3 was inactive despite a large enrichment in phospholipids. Furthermore, the PLD activity of activated thymocytes was negatively correlated to the proliferative response, with the exception of 20:5n-3-supplemented cells. These results support further our current hypothesis that PLD activity conveys antiproliferative signals in lymphoid cells, and suggest that 20:5n-3 inhibits thymocyte proliferation by a particular mechanism unrelated to that of the other FAs.