Incorporation, distribution, and turnover of arachidonic acid within membrane phospholipids of B220+ T cells from autoimmune-prone MRL-lpr/lpr mice.

Incorporation, distribution, and turnover of arachidonic acid within membrane phospholipids of B220+ T cells from autoimmune-prone MRL-lpr/lpr mice.
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在易免疫性MRL-LPR/LPR小鼠的B220+ T细胞的膜磷脂内掺入,分布和周转。

DOI:
10.1084/jem.171.3.787
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发表时间:
1990-03-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Santoro TJ
Santoro TJ
中科院分区:
其他
文献类型:
--
作者:
Tomita-Yamaguchi M;Babich JF;Baker RC;Santoro TJ

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含AA的磷酸甘油酯在T细胞膜内的代谢导致第二信使的产生,第二信使似乎在跨膜信号转导中起关键作用。为了检验花生四烯酸-磷脂运动中的畸变与异常T细胞功能相关并可能潜在地促成异常T细胞功能的假设,检查了已知表现出免疫调节紊乱的细胞的膜甘油脂内AA的掺入、分布和周转。使用来自自身免疫性MRL-1 pr/1 pr小鼠的Thy-1+、Ly-1+、L3 T4-、Lyt-2-、B220+ T细胞作为细胞模型。与优先将标记的AA掺入磷脂酰胆碱(PC)的对照淋巴结T细胞相反,B220+ T细胞显示出将[3 H]花生四烯酸分配到磷脂酰肌醇(PI)的偏好。B220+ T细胞中花生四烯酸-磷脂池是正常的。与对照细胞相比,B220+ T细胞中[3 H]花生四烯酸酰-PI的组成性周转显著增加,[3 H]花生四烯酸酯-PC的组成性周转显著减少。使用膜匀浆B220+ T细胞表现出溶血PI水平的功能性增加。完整的B220+ T细胞预标记与[3 H]肌醇和培养的情况下,刺激与外源性抗原或有丝分裂原,表现出增加生产溶血PI。这些数据表明,[3 H]花生四烯酸-PI在B220+ T细胞中的优先形成是由于膜磷脂酶A2活性引起的组成型PI周转大大增加的结果。它仍然可能是花生四烯酸内的磷脂B220+ T细胞的运动的干扰发挥作用的异常免疫活性的表达。
The metabolism of AA-containing phosphoglycerides within T cell membranes leads to the generation of second messengers that appear to play a crucial role in transmembrane signal transduction. To test the hypothesis that aberrations in the movement of arachidonoyl- phospholipids are associated with and may potentially contribute to abnormal T cell function, the incorporation, distribution, and turnover of AA within the membrane glycerolipids of cells that are known to exhibit immunoregulatory disturbances was examined. Thy-1+, Ly-1+, L3T4- , Lyt-2-, B220+ T cells from autoimmune MRL-lpr/lpr mice were used as the cellular model. In contrast to control lymph node T cells, which preferentially incorporate labeled AA into phosphatidylcholine (PC), B220+ T cells displayed a predilection for distributing [3H]arachidonate into phosphatidylinositol (PI). The arachidonoyl- phospholipid pools were normal in B220+ T cells. The constitutive turnover of [3H]arachidonoyl-PI was significantly enhanced and that of [3H]arachidonate-PC substantially reduced in B220+ T cell compared with control cells. Using membrane homogenates B220+ T cells demonstrated a functional increase in the levels of lyso-PI. Intact B220+ T cells prelabeled with [3H]myoinositol and cultured in the absence of stimulation with exogenous antigens or mitogens, exhibited increased production of lyso-PI. The data indicate that the preferential formation of [3H]arachidonoyl-PI in B220+ T cells is the result of greatly increased, constitutive PI turnover that appears to be due to a membrane phospholipase A2 activity. It remains possible that disturbances in the movement of arachidonate within phospholipids of B220+ T cells play a role in the expression of aberrant immunological activity.