Albert D H, Snyder F
Biochim Biophys Acta. 1984 Oct 24;796(1):92-101. doi: 10.1016/0005-2760(84)90242-x.
Platelet activating factor and the bioactive metabolites of arachidonic acid are secreted by alveolar macrophages in response to stimulation by phagocytic agents or calcium ionophore. We have previously shown a deacylation-acetylation sequence in the formation of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) from alkylacyl-(long chain)-GPC (Albert, D.H. and Snyder, F. (1983) J. Biol. Chem. 258, 97-102). This sequence may be an important source of 20:4 during inflammatory reactions since, in alveolar macrophages, the ether lipid precursor of PAF represents 35% of the choline glycerophospholipids and has a much higher content (35%) of 20:4 in the sn-2 position than does diacyl-GPC (17%). Alveolar macrophages prelabeled with 14C-labeled fatty acids (16:0, 18:1, 18:2 and 20:4) and [1-3H]alkyllyso-GPC were used to study the release of fatty acids from ether-linked and diacyl phospholipids. Each of these fatty acids was incorporated primarily into the choline glycerophospholipids of alveolar macrophages. The release of 20:4 from macrophage phospholipids was increased by treatment of the labeled cells with the calcium ionophore A23187 (2 microM) or zymosan (1 mg/ml), whereas the release of 16:0, 18:1 and 18:2 was not increased above control levels by either stimuli. Although more of the labeled 20:4 is released from the diacyl-GPC (50% of the total released), substantial amounts (44%) of 20:4 are derived from alkylacyl-GPC after incubating the stimulated cells for 60 min. The loss of 20:4 continued from the diacyl species throughout the incubation period studied, whereas a slower net release of 20:4 lost from the alkylacyl-GPC fraction was evident after 2 h. We conclude that the deacylation-reacylation cycle is an important aspect of the metabolism of 20:4 and alkylacyl-GPC during inflammatory stimulation of alveolar macrophages and that the deacylation of this ether-linked phospholipid (which is the first step in the formation of PAF) is responsible for a significant amount of the 20:4 released.
血小板活化因子和花生四烯酸的生物活性代谢产物是肺泡巨噬细胞在吞噬剂或钙离子载体刺激下分泌的。我们之前已经证明，从烷基酰基-（长链）-甘油磷酸胆碱（GPC）形成1-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱（PAF）的过程中存在脱酰化-乙酰化序列（阿尔伯特，D.H.和斯奈德，F.（1983年）《生物化学杂志》258卷，97-102页）。这个序列可能是炎症反应期间20:4的一个重要来源，因为在肺泡巨噬细胞中，PAF的醚脂前体占胆碱甘油磷脂的35%，并且在sn-2位置的20:4含量（35%）比二酰基-GPC（17%）高得多。用14C标记的脂肪酸（16:0、18:1、18:2和20:4）以及[1-3H]烷基溶血-GPC预标记的肺泡巨噬细胞用于研究脂肪酸从醚键连接和二酰基磷脂中的释放。这些脂肪酸中的每一种主要都掺入到肺泡巨噬细胞的胆碱甘油磷脂中。用钙离子载体A23187（2 microM）或酵母聚糖（1 mg/ml）处理标记细胞后，巨噬细胞磷脂中20:4的释放增加，而16:0、18:1和18:2的释放没有因任何一种刺激而高于对照水平。虽然更多的标记20:4是从二酰基-GPC中释放的（占总释放量的50%），但在刺激细胞孵育60分钟后，大量（44%）的20:4来自烷基酰基-GPC。在整个研究的孵育期间，二酰基种类中的20:4持续丢失，而在2小时后，从烷基酰基-GPC部分丢失的20:4的净释放明显较慢。我们得出结论，脱酰化-再酰化循环是肺泡巨噬细胞炎症刺激期间20:4和烷基酰基-GPC代谢的一个重要方面，并且这种醚键连接的磷脂（这是PAF形成的第一步）的脱酰化导致了大量20:4的释放。
