Clemens Natascha, Frauenknecht Katrin, Katzav Aviva, Sommer Clemens, von Landenberg Philipp
Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany.
Ann N Y Acad Sci. 2009 Sep;1173:805-13. doi: 10.1111/j.1749-6632.2009.04632.x.
It has been shown that stimulation of endothelial cells and monocytes by antiphospholipid antibodies leads to a prothrombotic state involving upregulation of tissue factor (TF). We examined the in vitro effects of IgG fractions from patients with antiphospholipid syndrome (APS) and of a beta-2-glycoprotein 1-independent human monoclonal antiphospholipid antibody (HL-5B) on human umbilical vein endothelial cells (HUVEC) in comparison to untreated cell controls and to exposure to monoclonal IgG control antibody. We also examined the effect of recombinant monocyte chemoattractant protein-1 (MCP-1) on peripheral blood monocytes. Stimulation of endothelial cells with APS IgG fractions or HL-5B resulted in time-dependent upregulation of MCP-1 mRNA and protein expression. Stimulation with HL-5B also led to time-dependent upregulation of interleukin (IL)-8 and intracellular adhesion molecule-1 (ICAM-1) mRNA and IL-8 protein expressions. Stimulation of monocytes with recombinant MCP-1 resulted in an upregulation of TF mRNA and TF protein. In conclusion these results might represent a mechanism for antiphospholipid antibody-mediated thrombosis in APS patients.
研究表明,抗磷脂抗体刺激内皮细胞和单核细胞会导致一种促血栓形成状态,其中涉及组织因子(TF)的上调。我们检测了抗磷脂综合征(APS)患者的IgG组分以及一种β2糖蛋白1非依赖性人源单克隆抗磷脂抗体(HL-5B)对人脐静脉内皮细胞(HUVEC)的体外作用,并与未处理的细胞对照以及暴露于单克隆IgG对照抗体的情况进行比较。我们还检测了重组单核细胞趋化蛋白-1(MCP-1)对外周血单核细胞的作用。用APS IgG组分或HL-5B刺激内皮细胞会导致MCP-1 mRNA和蛋白表达随时间上调。用HL-5B刺激还会导致白细胞介素(IL)-8和细胞间黏附分子-1(ICAM-1)mRNA以及IL-8蛋白表达随时间上调。用重组MCP-1刺激单核细胞会导致TF mRNA和TF蛋白上调。总之,这些结果可能代表了APS患者中抗磷脂抗体介导血栓形成的一种机制。