Biosynthetic labelling of platelet activating factor from radioactive acetate by stimulated platelets
Biosynthetic labelling of platelet activating factor from radioactive acetate by stimulated platelets
复制标题
受刺激血小板生物合成标记放射性醋酸盐血小板激活因子
DOI：
10.1038/289312a0
复制
发表时间：
1981
期刊：
影响因子：
64.8
通讯作者：
L. Douste‐Blazy
中科院分区：
文献类型：
--
作者：
H. Chap;G. Mauco;M. Simon;J. Benveniste;L. Douste‐Blazy
血小板活化因子（PAF-醋酸酯）是一种在体外和体内免疫挑战条件下由嗜碱性粒细胞释放的化学介质1 -5。PAF-醋酸酯诱导不同物种血小板的聚集和分泌3，6，7，因此可能与各种免疫形式的组织损伤有关8，9。已经描述了这种介质的其他来源，包括巨噬细胞10和血小板11。由于在后一种情况下释放的PAF-乙酸酯的量足以支持血小板聚集11，并且由于PAF-乙酸酯引起的血小板聚集不需要ADP分泌或血栓烷生物合成12，因此建议将PAF-乙酸酯作为假定的血小板聚集第三途径的介质11。通过脂肪酶对PAF-乙酸酯进行的结构分析表明，它可能是一种甘油磷脂，在1位没有酯键，在2位带有酯化的脂肪酸13。这为磷脂显示出强大的化学介质的特性提供了第一个证据。基于几条证据，最近提出1 - 0-烷基-2-乙酰基-sn-甘油基-3-乙酰基-磷酸胆碱（1-烷基-2-乙酰基-GPC）作为介体的化学结构，因此称为PAF-乙酸酯14，15。由于PAF-乙酸合成在活化血小板中发生得相当早，因此PAF-乙酸形成的最有效途径之一可能涉及相应溶血衍生物（1-烷基-GPC）的快速乙酰化。我们现在提出的证据表明，血小板激活的离子载体A23187能够将乙酸酯的1-烷基-2-乙酰基-GPC和1-酰基-2-乙酰基-GPC的混合物;前者支持PAF-乙酸酯的生物活性。
Platelet activating factor (PAF-acether) is a chemical mediator released by basophils in in vitro and in vivo conditions of immunological challenge1–5. PAF-acether induces aggregation and secretion of platelets from different species3,6,7 and could thus be implicated in various immunological forms of tissue injury8,9. Other sources have been described for this mediator, including macrophages10 and platelets11. As the amounts of PAF-acether released in the latter case are sufficient to support the platelet aggregation11 and as platelet aggregation by PAF-acether does not require ADP secretion or thromboxane biosynthesis12, PAF-acether was proposed as the mediator of the putative third pathway of platelet aggregation11. Structural analysis of PAF-acether by lipases indicated that it could be a glycerophospholipid devoid of an ester linkage at the 1-position and bearing a fatty acid esterified at the 2-position13. This has provided the first evidence for a phospholipid displaying the properties of a powerful chemical mediator. Based on several lines of evidence, l-O-alkyl-2-acetyl-sn-glyceryl-3-phos-phorylcholine (l-alkyl-2-acetyl-GPC) was recently proposed as the chemical structure of the mediator, hence the term PAF-acether14,15. As PAF-acether synthesis occurs rather early in activated platelets, one of the most efficient pathways of PAF-acether formation could involve a rapid acetylation of the corresponding lysoderivative (1-alkyl-GPC). We now present evidence that platelets activated by ionophore A23187 are able to incorporate acetate into a mixture of l-alkyl-2-acetyl-GPC and l-acyl-2-acetyl-GPC; the former supports the biological activity of PAF-acether.