Factors that influence the proportions of platelet-activating factor and 1-acyl-2-acetyl-sn-glycero-3-phosphocholine synthesized by the mast cell.
Factors that influence the proportions of platelet-activating factor and 1-acyl-2-acetyl-sn-glycero-3-phosphocholine synthesized by the mast cell.
复制标题
影响肥大细胞合成的血小板活化因子和1-酰基-2-乙酰基-sn-甘油-3-磷酸胆碱比例的因素。
DOI：
10.1042/bj2860497
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Chilton,FH
中科院分区：
文献类型：
--
作者：
Triggiani,M;Fonteh,AN;Chilton,FH
最近的研究表明，炎症细胞可以根据它们产生的2-乙酰化磷脂[1-radyl-2-乙酰基-sn-甘油-3-磷酸胆碱(GPC)]的类型而分为两组：主要产生血小板激活因子(PAF)的细胞和主要产生其1-酰基类似物(1-酰基-2-乙酰基-GPC；AAGPC)的细胞[Triggiani，Schlemer，Warner&Chilton(1991)J.147,660-666]。本研究探讨了在小鼠骨髓来源的肥大细胞(BMMC)中调节这两种分子产生的因素。初步实验表明，PAF和AAGPC被BMMC通过两条途径以不同的方式降解：第一条途径是AAGPC所独有的，涉及1-酰基水解酶，它去除了分子sn-1位的长链；第二条途径是AAGPC和PAF共同的，涉及乙酰水解酶，它去除了这两个分子sn-2位的乙酸酯。接下来设计了实验，以确定AAGPC和PAF的差异分解代谢可以被消除的条件，以揭示调节AAGPC和PAF产生的比例的其他因素。苯甲基磺酰氟(PMSF)完全阻断了1-酰基水解酶的活性，而对乙酰水解酶活性几乎没有影响，从而消除了AAGPC特有的分解代谢途径的影响。此外，PMSF不改变磷脂亚类花生四烯酸的释放。PMSF处理的BMMC产生的AAGPC数量高于PAF处理的BMMC。在PMSF处理的BMMC中检测到的AAGPC/PAF比率与1-酰基/1-烷基连接的磷脂酰胆碱(PC)所含和释放的花生四烯酸的比率非常相似。BMMC加入花生四烯酸培养3d后，PC中总花生四烯酸含量增加，1-酰基-2-花生四烯酸-GPC/1-烷基-2-花生四烯酸-GPC比值增加。这些变化导致BMMC中1-radyl-2-乙酰基-GPC总量和AAGPC/PAF比值平行且显著增加。这些数据表明，炎症细胞产生的AAGPC/PAF的比例至少受两个因素的调节：(1)这两个分子的不同分解代谢；(2)花生四烯酸在1-酰基和1-烷基-2-花生四烯基-GPC中的分布。这些观察结果支持AAGPC和PAF生物合成的共同途径的概念，其中两个前体分子分别是1-酰基-2-花生四烯基-GPC和1-烷基-2-花生四烯基-GPC。
Recent studies have demonstrated that inflammatory cells can be divided into two groups depending on the type of 2-acetylated phospholipids [1-radyl-2-acetyl-sn-glycero-3-phosphocholine (GPC)] they produce: those that produce predominantly platelet-activating factor (PAF), and those that produce predominantly its 1-acyl analogue (1-acyl-2-acetyl-GPC; AAGPC) [Triggiani, Schleimer, Warner & Chilton (1991) J. Immunol. 147, 660-666]. The present study has examined the factors that regulate the production of these two molecules in mouse bone marrow-derived mast cells (BMMC). Initial experiments indicated that PAF and AAGPC were catabolized by BMMC in a differential manner via two pathways: the first, exclusive for AAGPC, involved a 1-acyl hydrolase that removed the long chain at the sn-1 position of the molecule, and the second, common to AAGPC and PAF, involved acetylhydrolase that removed the acetate at the sn-2 position of the two molecules. Experiments were next designed to identify conditions where the differential catabolism of AAGPC and PAF could be eliminated in order to uncover other factors that regulate the proportions of AAGPC and PAF produced. Phenylmethanesulphonyl fluoride (PMSF) completely blocked the 1-acylhydrolase activity while having little or no effect on the acetyl hydrolase activity, thereby eliminating the influence of the catabolic pathway unique to AAGPC. Moreover, PMSF did not alter the release of arachidonic acid from phospholipid subclasses. PMSF-treated BMMC produced larger quantities of AAGPC than of PAF. The AAGPC/PAF ratio detected in PMSF-treated BMMC was very similar to the ratio of arachidonate contained in and released from 1-acyl-/1-alkyl-linked phosphatidylcholine (PC). BMMC supplemented with arachidonic acid in culture for 3 days increased their total arachidonic acid content in PC as well as the ratio of 1-acyl-2-arachidonoyl-GPC to 1-alkyl-2-arachidonoyl-GPC. These changes resulted in parallel and significant increases in both the total amount of 1-radyl-2-acetyl-GPC and the AAGPC/PAF ration in BMMC. These data indicate that the AAGPC/PAF ratio produced by inflammatory cells is regulated by at least two factors: (1) differential catabolism of these two molecules, and (2) the distribution of arachidonate in 1-acyl- and 1-alkyl-2-arachidonyl-GPC. These observations support the concept of a common pathway for AAGPC and PAF biosynthesis in which the two precursor molecules are 1-acyl-2-arachidonoyl-GPC and 1-alkyl-2-arachidonoyl-GPC, respectively.