Absence of unsaturated fatty acid synthesis in murine T lymphocytes.
Stearic acid is toxic for T lymphocytes in vitro but has little effect on B lymphocytes. To investigate the molecular basis for this difference, purified murine T and B lymphocytes were compared for their abilities to incorporate and metabolize stearic acid. Unstimulated T and B cells incorporated identical amounts of stearic acid into six different phospholipids and four neutral lipids. After mitogen stimulation, fatty acid uptake was increased in both lymphocyte types, but cell-specific differences were seen in the distribution of stearic acid among the various cellular lipids. Doses of stearic acid that selectively inhibited T-cell proliferation resulted in a 5-fold greater accumulation of distearoylphosphatidylcholine in T cells than in B cells. Whereas T cells did not desaturate the exogenously derived stearic acid, up to 25% of the saturated fatty acid was converted to oleic acid in B cells. These findings suggested a deficiency of stearoyl-CoA desaturase (acyl-CoA, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.5) activity in T cells, which was confirmed by subsequent studies. Cell-free extracts from B cells displayed nearly 20-fold more stearoyl-CoA desaturase activity than T-cell extracts, and the level of stearoyl-CoA desaturase mRNA was 30-fold higher in B cells. Collectively, our data indicate that murine T cells are deficient in unsaturated fatty acid synthesis. The deficiency of stearoyl-CoA desaturase in T cells may represent the basis for the differing sensitivities of T and B lymphocytes to inhibition by saturated fatty acids.
Buttke
T M
TM
Department of Microbiology and Immunology, East Carolina University, School of Medicine, Greenville, NC 27858.
Van Cleave
S
S
Steelman
L
L
McCubrey
J A
JA
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D004247:DNA / Q000096:biosynthesis; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D007700:Kinetics; D008055:Lipids / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D010743:Phospholipids / Q000096:biosynthesis; D013229:Stearic Acids / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D010743:Phospholipids; D013229:Stearic Acids; C031183:stearic acid; D004247:DNA; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; D013936:Thymidine