Activation of cultured vascular endothelial cells by antiphospholipid antibodies.
Activation of cultured vascular endothelial cells by antiphospholipid antibodies.
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DOI：
10.1172/jci118276
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发表时间：
1995-11
期刊：
影响因子：
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通讯作者：
R. Simantov;J. LaSala;S. Lo;A. Gharavi;L. Sammaritano;J. Salmon;R. Silverstein
中科院分区：
文献类型：
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作者：
R. Simantov;J. LaSala;S. Lo;A. Gharavi;L. Sammaritano;J. Salmon;R. Silverstein
循环抗磷脂抗体（aPL）与血栓形成、复发性流产和血小板减少综合征有关。我们已经证明了培养的人脐静脉内皮细胞（HUVEC）的抗心磷脂抗体（ACL）患者的IgG的激活。与来自高滴度aCL患者的纯化IgG（100微克/ml）一起孵育HUVEC 4小时，诱导单核细胞粘附比与来自正常受试者的IgG一起孵育的HUVEC中所见的单核细胞粘附增加2.3倍。aCL的作用不归因于LPS污染、Fc受体或免疫复合物。单核细胞粘附不诱导时，在无血清培养基中加入的ACL，但通过添加纯化的β 2GP 1，以前描述为一个必要的辅因子的ACL反应性恢复。当与HUVEC孵育时，针对β 2GP 1的纯化的兔多克隆IgG也诱导单核细胞粘附。用心磷脂预吸附患者血清可使单核细胞粘附减少60%。免疫荧光显微镜显示，与患者IgG孵育的内皮细胞表达细胞粘附分子，包括E-选择素，血管细胞粘附分子-1，和细胞内粘附分子-1。这些数据支持aPL激活血管内皮细胞，从而导致血栓形成前状态的假设。
Circulating antiphospholipid antibodies (aPL) are associated with a syndrome of thrombosis, recurrent fetal loss, and thrombocytopenia. We have demonstrated the activation of cultured human umbilical vein endothelial cells (HUVEC) by IgG from patients with anticardiolipin antibodies (aCL). Incubation of HUVEC for 4 h with purified IgG (100 micrograms/ml) from patients with high-titer aCL induced a 2.3-fold increase in monocyte adhesion over that seen in HUVEC incubated with IgG's from normal subjects. The effect of aCL was not attributable to LPS contamination, Fc receptors, or immune complexes. Monocyte adhesion was not induced when the aCL were added in serum-free media but was restored by the addition of purified beta 2GP1, previously described as a necessary cofactor for aCL reactivity. Purified rabbit polyclonal IgG raised against beta 2GP1 also induced monocyte adhesion when incubated with HUVEC. Preadsorption of patient serum with cardiolipin reduced monocyte adhesion by 60%. Immunofluorescent microscopy demonstrated that endothelial cells incubated with patient IgG expressed cell adhesion molecules, including E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. These data support the hypothesis that aPL activate vascular endothelial cells, thereby leading to a pro-thrombotic state.