Silver R K, Adler L, Hickman A R, Hageman J R
Division of Maternal-Fetal Medicine, Evanston Hospital, IL 60201.
Am J Obstet Gynecol. 1991 Dec;165(6 Pt 1):1748-52. doi: 10.1016/0002-9378(91)90028-p.
Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis.
循环中的抗磷脂与复发性流产有关，其机制涉及胎盘和蜕膜血栓形成。我们推测，血小板激活因子，一种由血管内皮合成的自分泌物质，可能通过其促进血小板聚集和纤维蛋白沉积的能力介导这一现象。另外，抗磷脂抗体可能通过抑制前列环素的合成发挥促凝作用。为了评估这些理论，将（从人脐静脉采集的）内皮细胞培养至汇合，并与20%浓度的抗心磷脂抗体阳性和阴性人血清以及胎牛血清一起孵育48小时。孵育后，用10μmol/ml钙离子载体A23187（血小板激活因子和前列环素合成的激动剂）刺激培养孔。通过氚化乙酸掺入、磷脂提取、薄层色谱和闪烁分光光度法测量细胞内血小板激活因子。与抗心磷脂抗体阴性血清（18,600±3316 dpm）或胎牛血清（19,014±4233 dpm；方差分析，p = 0.033）相比，在与抗心磷脂抗体阳性血清孵育的培养物中发现血小板激活因子合成增强（每分钟25,544±2604次衰变，平均值±标准差）。在类似实验中，通过测量培养上清液中前列环素的主要代谢产物6-酮-前列腺素F1α来测定前列环素的合成。抗心磷脂抗体阳性培养物与对照培养物之间未观察到差异（方差分析，p = 0.90）。我们得出结论，在这个内皮细胞模型中，抗心磷脂抗体阳性血清增强了离子载体介导的血小板激活因子合成，但对前列环素的产生没有明显影响。这些发现表明血小板激活因子在抗心磷脂抗体介导的血管血栓形成中可能发挥作用。
