Ando S, Tomita-Yamaguchi T, Santoro T J
Department of Medicine, University of Colorado Health Sciences Center, Denver.
Biochim Biophys Acta. 1993 Apr 30;1181(2):141-7. doi: 10.1016/0925-4439(93)90103-8.
To test the hypothesis that T-cells which exhibit abnormal immunological behavior manifest derangements in the de novo synthesis of phospholipids, the utilization of [3H]palmitic acid in B220+ T-cells from autoimmune MRL-lpr/lpr mice was investigated. The rate of incorporation of [3H]palmitic acid into membrane phospholipids was markedly increased in intact B220+ T-cells compared to that in T-cells from immunologically normal mice. The activities of two key enzymes involved in the de novo synthesis of palmitoyl-phospholipids, acyl-coenzyme (CoA) ligase and acyl-CoA; sn-glycerol-3-phosphate acyl transferase, were significantly higher in homogenates from B220+ T-cell membranes compared with those in controls. Despite these findings, the molar concentration of individual palmitoyl glycerolipids was equivalent in the membranes of B220+ T-cells and control lymph node T-cells. The results indicate that T-cells from lupus mice exhibit complex defects in the biosynthesis and turnover of membrane phospholipids and suggest the possibility that these aberrations contribute to T-cell dysfunction in autoimmune diseases.
为了验证表现出异常免疫行为的T细胞在磷脂从头合成中存在紊乱这一假设,研究了来自自身免疫性MRL-lpr/lpr小鼠的B220⁺ T细胞中[³H]棕榈酸的利用情况。与免疫正常小鼠的T细胞相比,完整的B220⁺ T细胞中[³H]棕榈酸掺入膜磷脂的速率显著增加。参与棕榈酰磷脂从头合成的两种关键酶,即酰基辅酶(CoA)连接酶和酰基辅酶A;sn-甘油-3-磷酸酰基转移酶的活性,在B220⁺ T细胞膜匀浆中明显高于对照组。尽管有这些发现,但B220⁺ T细胞膜和对照淋巴结T细胞膜中单个棕榈酰甘油脂质的摩尔浓度相当。结果表明,狼疮小鼠的T细胞在膜磷脂的生物合成和周转方面表现出复杂的缺陷,并提示这些异常可能导致自身免疫性疾病中的T细胞功能障碍。