Low-molecular-weight heparin inhibition in classical complement activaton pathway during pregnancy
Low-molecular-weight heparin inhibition in classical complement activaton pathway during pregnancy
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DOI：
10.1016/j.thromres.2009.11.030
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发表时间：
2010-05-01
影响因子：
7.5
通讯作者：
Calabrese, Graciela C.
中科院分区：
文献类型：
--
作者：
Oberkersch, Roxana;Attorresi, Alejandra I.;Calabrese, Graciela C.
简介：低分子量肝素在临床上用于预防与血栓前疾病相关的妊娠并发症，特别是抗磷脂综合征。然而，最近的研究表明，肝素可能会对胎盘滋养层产生直接影响，独立于其抗凝活性。此外，肝素可防止体内补体激活，并保护小鼠免受妊娠并发症的影响。材料和方法：通过体外试验和接受治疗剂量预防的孕妇分析肝素对经典补体激活途径的抑制作用通过抗体致敏绵羊红细胞溶血（CH（50）试验）皮下注射低分子量肝素（40 mg/天）。低分子量肝素和补体级联C1复合物的C1 q亚基之间的特异性相互作用允许分离肝素的小亚群（8.03 +/- 1.20 μ g %），其抗活化因子X活性比起始材料大4倍以上。这个亚群可能是负责在体外抑制的经典补体激活途径的抗体致敏绵羊红细胞的总溶血评价。约60 μ g/ml的低分子量肝素需要达到50%的溶血。经典的补体途径抑制肝素治疗的孕妇中的检测需要第一次激活与聚集的人IgG.Conclusions：我们得出结论，低分子量肝素和C1 q之间的相互作用可能是相关的，不仅在补体依赖性，但也在负责预防妊娠损失的补体非依赖性炎症机制。爱思唯尔有限公司出版
Introduction: Low-molecular-weight heparin is used clinically for the prevention of pregnancy complications associated with prothrombotic disorders, particularly anti-phospholipid syndrome. Nevertheless, recent studies have suggested that heparin may exert direct effects on the placental trophoblast, independently of its anticoagulant activity. In addition, heparin prevents complement activation in vivo and protects mice from pregnancy complications.Materials and Methods: The inhibition of the classical complement activation pathway by heparin was analyzed by means of in vitro assays and in pregnant women receiving prophylaxis with therapeutic doses (40 mg/day) of subcutaneous low molecular weight heparin by haemolysis of antibody-sensitized sheep erythrocytes (CH(50) assay).Results: The specific interaction between low-molecular-weight heparin and the C1q subunit of the C1 complex of the complement cascade allowed the isolation of a small subpopulation of heparin (8.03 +/- 1.20 mu g %), with an anti-activated factor X activity more than four times greater than the starting material. This subpopulation could be responsible for the in vitro inhibition of the classical complement activation pathway evaluated by the total haemolysis of antibody-sensitized sheep erythrocytes. About 60 mu g/ml of low molecular weight heparin was needed to achieve 50% of haemolysis. The detection of the classical complement pathway inhibition in pregnant women treated with heparin required a first activation with aggregated human IgG.Conclusions: We concluded that the interaction between low-molecular-weight heparin and C1q could be relevant not only in the complement-dependent, but also in the complement-independent inflammation mechanisms responsible for the prevention of pregnancy loss. Published by Elsevier Ltd.