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血小板激活因子(Paf-乙酰醚)的生物合成。VII. 人白细胞中血小板激活因子的前体和乙酰转移酶活性

Biosynthesis of Paf-acether (platelet-activating factor). VII. Precursors of Paf-acether and acetyl-transferase activity in human leukocytes.

作者信息

Jouvin-Marche E, Ninio E, Beaurain G, Tence M, Niaudet P, Benveniste J

出版信息

J Immunol. 1984 Aug;133(2):892-8.

PMID:6736649
Abstract

Human polymorphonuclear neutrophils, monocytes, and lymphocytes were studied for their ability to synthesize Paf-acether when stimulated with the ionophore A 23187 (Io) or with specific secretagogues. When stimulated with Io, neutrophils produced 100 +/- 8.5 pmol Paf-acether 1 X 10(6) cells (mean +/- 1 SD, n = 5); monocytes were less efficient (44 +/- 3.3 pmol Paf-acether/1 X 10(6) cells), whereas lymphocytes were practically unable to form this mediator (1.0 +/- 0.4 pmol Paf-acether/1 X 10(6) cells). Neutrophils and monocytes released in the extracellular medium 49 and 37% of Paf-acether that they formed, respectively. We attempted to correlate the amount of Paf-acether produced by the various cell types with that of its precursors, 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine and 1-O-alkyl-sn-glycero-3-phosphocholine (2-lyso Paf-acether). In the three cell types, the amount of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine was sufficient to ensure the formation of 2-lyso Paf-acether and consequently that of Paf-acether. The quantity of 2-lyso Paf-acether formed appeared to be the limiting factor only in the case of the neutrophils. These cells increased their synthesis of Paf-acether in the presence of exogenous 2-lyso Paf-acether. To investigate the failure of lymphocytes to produce the mediator, the acetylating step of Paf-acether formation was studied, and we found a very weak activity (0.5 +/- 0.1 nmol Paf-acether/10 min/mg protein) in this cell type as opposed to monocytes (4.0 +/- 2.3 nmol Paf-acether/10 min/mg protein) and neutrophils (17.8 +/- 5.3 nmol Paf-acether/10 min/mg protein). These activities were doubled in Io-stimulated cells. Thus, the modulation of acetyl-transferase activity appears to be a key step in the regulation of Paf-acether biosynthesis. Also, the availability of 2-lyso Paf-acether could regulate Paf-acether synthesis in human neutrophils.

摘要

研究了人类多形核中性粒细胞、单核细胞和淋巴细胞在受到离子载体A 23187(Io)或特定促分泌剂刺激时合成血小板活化因子(Paf - 乙酰醚)的能力。当用Io刺激时,中性粒细胞每1×10⁶个细胞产生100±8.5 pmol的Paf - 乙酰醚(平均值±1标准差,n = 5);单核细胞的效率较低(44±3.3 pmol Paf - 乙酰醚/1×10⁶个细胞),而淋巴细胞几乎无法形成这种介质(1.0±0.4 pmol Paf - 乙酰醚/1×10⁶个细胞)。中性粒细胞和单核细胞分别将它们形成的Paf - 乙酰醚的49%和37%释放到细胞外介质中。我们试图将不同细胞类型产生的Paf - 乙酰醚的量与其前体1 - O - 烷基 - 2 - 酰基 - sn - 甘油 - 3 - 磷酸胆碱和1 - O - 烷基 - sn - 甘油 - 3 - 磷酸胆碱(2 - 溶血Paf - 乙酰醚)的量相关联。在这三种细胞类型中,1 - O - 烷基 - 2 - 酰基 - sn - 甘油 - 3 - 磷酸胆碱的量足以确保2 - 溶血Paf - 乙酰醚的形成,从而确保Paf - 乙酰醚的形成。仅在中性粒细胞的情况下,形成的2 - 溶血Paf - 乙酰醚的量似乎是限制因素。在存在外源性2 - 溶血Paf - 乙酰醚的情况下,这些细胞增加了它们对Paf - 乙酰醚的合成。为了研究淋巴细胞无法产生这种介质的原因,研究了Paf - 乙酰醚形成的乙酰化步骤,我们发现这种细胞类型中的活性非常弱(0.5±0.1 nmol Paf - 乙酰醚/10分钟/毫克蛋白质),与单核细胞(4.0±2.3 nmol Paf - 乙酰醚/10分钟/毫克蛋白质)和中性粒细胞(17.8±5.3 nmol Paf - 乙酰醚/10分钟/毫克蛋白质)相反。在Io刺激的细胞中,这些活性增加了一倍。因此,乙酰转移酶活性的调节似乎是Paf - 乙酰醚生物合成调节中的关键步骤。此外,2 - 溶血Paf - 乙酰醚的可用性可以调节人类中性粒细胞中Paf - 乙酰醚的合成。

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