Buttke T M, Van Cleave S, Steelman L, McCubrey J A
Department of Microbiology and Immunology, East Carolina University, School of Medicine, Greenville, NC 27858.
Proc Natl Acad Sci U S A. 1989 Aug;86(16):6133-7. doi: 10.1073/pnas.86.16.6133.
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.
硬脂酸在体外对T淋巴细胞有毒性,但对B淋巴细胞影响较小。为了研究这种差异的分子基础,对纯化的小鼠T淋巴细胞和B淋巴细胞摄取及代谢硬脂酸的能力进行了比较。未受刺激的T细胞和B细胞将等量的硬脂酸掺入六种不同的磷脂和四种中性脂质中。丝裂原刺激后,两种淋巴细胞类型的脂肪酸摄取均增加,但在各种细胞脂质中硬脂酸的分布存在细胞特异性差异。选择性抑制T细胞增殖的硬脂酸剂量导致二硬脂酰磷脂酰胆碱在T细胞中的积累比在B细胞中高5倍。T细胞不会使外源来源的硬脂酸去饱和,而在B细胞中高达25%的饱和脂肪酸会转化为油酸。这些发现表明T细胞中硬脂酰辅酶A去饱和酶(酰基辅酶A,氢供体:氧氧化还原酶,EC 1.14.99.5)活性不足,后续研究证实了这一点。B细胞的无细胞提取物显示出的硬脂酰辅酶A去饱和酶活性比T细胞提取物高近20倍,且B细胞中硬脂酰辅酶A去饱和酶mRNA水平高30倍。总体而言,我们的数据表明小鼠T细胞在不饱和脂肪酸合成方面存在缺陷。T细胞中硬脂酰辅酶A去饱和酶的缺乏可能是T淋巴细胞和B淋巴细胞对饱和脂肪酸抑制敏感性不同的基础。