抗β2糖蛋白1抗体对内皮细胞中组织因子、血栓调节蛋白和纤溶酶原激活物抑制剂-1表达的促血栓形成作用
Prothrombotic Effect of Anti-beta-2 Glycoprotein-1 Antibodies on the Expression of Tissue Factor, Thrombomodulin, and Plasminogen Activator Inhibitor-1 in Endothelial Cells.
作者信息
Dharma Rahajuningsih, Tambunan Karmel L, Isbagyo Harry, Dewi Betty E, Acang Nuzirwan, Setiabudy Rianto, Aman Adi K
机构信息
Department of Clinical Pathology, Faculty of Medicine, University of Andalas - M. Djamil Hospital, Padang, Indonesia.
出版信息
Acta Med Indones. 2015 Jan;47(1):31-7.
AIM
to analyse the effects of immunoglobulin(Ig)G and IgM anti-beta-2 glycoprotein-1 (anti-2GP1) on the expression of tissue factor (TF), thrombomodulin (TM), and plasminogen activator inhibitor-1(PAI-1) of endothelial cells in the messenger RNA level.
METHODS
laboratory experimental study in human umbilical vein endothelial cells (HUVEC) was done at Cipto Mangunkusumo Hospital/Faculty of Medicine, Universitas Indonesia. Samples are purified IgG anti-2GP1 from six antiphospholipid syndrome (APS) patients serum and IgM anti-2GP1 from six APS patients serum. For controls, purified IgG from six normal human serum (IgM-NHS) and purified IgM from six normal human serum (IgM-NHS) were used. HUVEC were treated with purified IgG anti-2GP1, IgM anti-2GP1, IgG-NHS, IgM-NHS for four hours of incubation. We measured TF, TM, and PAI-1 of HUVEC in mRNA relative expression levels (before and after treatment) by real time reverse transcription polymerase chain reaction.
RESULTS
the mean value of TF, TM, and PAI-1 mRNA levels in HUVEC after treated with IgG anti-2GP1 compared to Ig-NHS were 3.14 (0.93)-, 0.31 (0.13)-, 5.33 (2.75)-fold respectively. In other hand, after treated with IgM anti-2GP1 compared to IgM-NHS, mRNA levels of TF, TM, and PAI-1 were 4.33 (1.98)-, 0.33 (0.22)-, 5.47 (2.64)-fold respectively. Before and after treatment with IgG anti-2GP1 showed significant differences of TF mRNA levels {1.09 (0.76) versus 3.14 (0.93), p=0.003}, TM mRNA levels {0.91 (0.11) versus 0.31(0.13), p=0.001}, and PAI-1 mRNA levels 0.93 (0.13) versus 5.33 (2.75), p=0.013}. Before and after treatment with IgM anti-2GP1 showed significant differences of TF mRNA levels {1.03 (0.11) versus 4.33 (1.98), p=0.008}, TM mRNA levels {0.93 (0.08) versus 0.33 (0.22, p=0.003}, and PAI-1 mRNA levels {1.02 (0.10) versus 5.47 (2.64), p=0.01}.
CONCLUSION
IgG anti-2GP1 and IgM anti-2GP1 increased TF and PAI-1 mRNA levels. However, IgG anti-2GP1 and IgM anti-2GP1 decreased TM mRNA levels. It proved that the mechanism of thrombosis in APS occurs through coagulation activation, reduction of fibrinolysis activity, and reduction of anticoagulant activity.
目的
分析免疫球蛋白（Ig）G和IgM抗β2糖蛋白1（抗2GP1）在信使核糖核酸水平对内皮细胞组织因子（TF）、血栓调节蛋白（TM）和纤溶酶原激活物抑制剂1（PAI-1）表达的影响。
方法
在印度尼西亚大学医学院西托·曼古库苏莫医院对人脐静脉内皮细胞（HUVEC）进行实验室实验研究。样本为从6例抗磷脂综合征（APS）患者血清中纯化的IgG抗2GP1和从6例APS患者血清中纯化的IgM抗2GP1。作为对照，使用从6例正常人血清中纯化的IgG（IgG-NHS）和从6例正常人血清中纯化的IgM（IgM-NHS）。将HUVEC用纯化的IgG抗2GP1、IgM抗2GP1、IgG-NHS、IgM-NHS处理4小时进行孵育。我们通过实时逆转录聚合酶链反应测量处理前后HUVEC中TF、TM和PAI-1的信使核糖核酸相对表达水平。
结果
与Ig-NHS相比，用IgG抗2GP1处理后HUVEC中TF、TM和PAI-1信使核糖核酸水平的平均值分别为3.14（0.93）倍、0.31（0.13）倍、5.33（2.75）倍。另一方面，与IgM-NHS相比，用IgM抗2GP1处理后，TF、TM和PAI-1的信使核糖核酸水平分别为4.33（1.98）倍、0.33（0.22）倍、5.47（2.64）倍。用IgG抗2GP1处理前后，TF信使核糖核酸水平{1.09（0.76）对3.14（0.93），p = 0.003}、TM信使核糖核酸水平{0.91（0.11）对0.31（0.13），p = 0.001}和PAI-1信使核糖核酸水平{0.93（0.13）对5.33（2.75），p = 0.013}有显著差异。用IgM抗2GP1处理前后，TF信使核糖核酸水平{1.03（0.11）对4.33（1.98），p = 0.008}、TM信使核糖核酸水平{0.93（0.08）对0.33（0.22），p = 0.003}和PAI-1信使核糖核酸水平{1.02（0.10）对5.47（2.64），p = 0.01}有显著差异。
结论
IgG抗2GP1和IgM抗2GP1增加TF和PAI-1信使核糖核酸水平。然而，IgG抗2GP1和IgM抗2GP1降低TM信使核糖核酸水平。这证明APS中血栓形成的机制是通过凝血激活、纤溶活性降低和抗凝活性降低发生的。
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