Kern H, Volk T, Knauer-Schiefer S, Mieth T, Rüstow B, Kox W J, Schlame M
Department of Anesthesiology and Intensive Care Medicine, University Hospital Charité, Humboldt-University, Schumannstr. 20-21, 10117 Berlin, Germany.
Biochim Biophys Acta. 1998 Oct 2;1394(1):33-42. doi: 10.1016/s0167-4889(98)00093-7.
Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented phospholipids which have similar bioactivities as the platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are produced upon PC oxidation, the active ingredients have not been identified. We synthesized several short-chain PCs which are known to be characteristic PC oxidation products to test their PAF-like activity. The synthetic PCs contained palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3), valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega-carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position. Biological activity was measured by: (1) increase of intracellular calcium in human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3) aggregation of human platelets. Specificity of the cellular response was tested by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic PC oxidation products activated both monocytes and platelets in a PAF-specific manner. The effective concentration varied with respect to assay system and chemical structure. In general, 1-hexadecyl-PCs were more effective than 1-palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1-palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl residues in sn-2 position, display PAF-like activity at micromolar concentrations.
不饱和磷脂酰胆碱（PC）的氧化会产生片段化的磷脂，这些磷脂具有与血小板活化因子（PAF，1-O-烷基-2-乙酰基-PC）相似的生物活性。由于PC氧化会产生大量分子种类，其活性成分尚未确定。我们合成了几种已知为PC氧化特征产物的短链PC，以测试它们的PAF样活性。合成的PC在sn-1位含有棕榈酰或十六烷基残基（均为C16），在sn-2位含有丙酰基（C3）、戊酰基（C5）、琥珀酰基（含ω-羧基的C4）、戊二酰基（含ω-羧基的C5）或辛二酰基（含ω-羧基的C8）残基。通过以下方法测量生物活性：（1）人单核细胞内钙离子的增加；（2）兔血小板中[3H]5-羟色胺的释放；（3）人血小板的聚集。通过PAF受体拮抗剂BN 52021和WEB 2086的抑制作用来测试细胞反应的特异性。合成的PC氧化产物以PAF特异性方式激活单核细胞和血小板。有效浓度因检测系统和化学结构而异。一般来说，1-十六烷基-PC比1-棕榈酰-PC更有效，而sn-2位链长增加会降低生物活性。然而，几种1-棕榈酰-PC在10-8至10-6 M的浓度下激活单核细胞。相比之下，血小板对1-棕榈酰-PC不太敏感。在2-戊酰基-PC（含ω-甲基的C5）和2-戊二酰基-PC（含ω-羧基的C5）之间未发现显著差异。数据表明，在sn-2位含有丙酰基、琥珀酰基或戊二酰基残基的PC氧化典型产物在微摩尔浓度下具有PAF样活性。
