Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo
Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo
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DOI：
10.1161/01.cir.99.15.1997
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发表时间：
1999-04-20
期刊：
影响因子：
37.8
通讯作者：
Harris, EN
中科院分区：
文献类型：
--
作者：
Pierangeli, SS;Colden-Stanfield, M;Harris, EN
Background-Antiphospholipid (aPL) antibodies are associated with thrombosis in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood.尽管 aPL 抗体已被证明可以在体外抑制蛋白 C 激活并激活内皮细胞 (EC)，但没有研究检验这些抗体是否在体内激活内皮细胞。因此，使用提睾肌在小鼠微循环模型中测试了来自 APS 患者的人亲和纯化 aPL (ap aPL) 抗体，该模型允许直接显微镜检查血栓形成和白细胞 (WBC) 与 EC 的粘附，作为体内 EC 激活的指示。在 aPL 暴露后，对人脐静脉内皮细胞 (HUVEC) 进行粘附分子表达，以确认体外 EC 激活。方法和结果 - 所有 6 种 aPL 抗体均显着增加 VCAM-1 的表达（2.3 至 4.4 倍），其中一种抗体还增加体外 HUVEC 上 E-选择素的表达（1.6 倍）。在体内实验中，与对照（14.4）相比，除 I 制剂外，每种 ap aPL 抗体均增加了 WBC 粘附（白细胞平均数量范围为 22.7 至 50.6），这与血栓形成增强相关（平均血栓大小范围为 1098 至 6476，对照为 594 μ m(2)）。结论 - aPL 抗体在体内激活 EC 可能会产生ECs 上的血栓前状态可能是 APS 血栓形成的第一个病理生理事件。
Background-Antiphospholipid (aPL) antibodies are associated with thrombosis in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. Although aPL antibodies have been shown to inhibit protein C activation and activate endothelial cells (ECs) in vitro, no study has examined whether these antibodies activate ECs in vivo. Therefore, human affinity-purified aPL (ap aPL) antibodies from APS patients were tested in a mouse model of microcirculation using the cremaster muscle that allows direct microscopic examination of thrombus formation and adhesion of white blood cells (WBCs) to ECs as an indication of EC activation in vivo. Adhesion molecule expression on human umbilical vein endothelial cells (HUVECs) after aPL exposure was performed to confirm EC activation in vitro.Methods and Results-All 6 ap aPL antibodies significantly increased the expression of VCAM-1 (2.3- to 4.4-fold), with one of the antibodies also increasing the expression of E-selectin (1.6-fold) on HUVECs in vitro. In the in vivo experiments, each ap aPL antibody except for I preparation increased WBC sticking (mean number of WBCs ranged from 22.7 to 50.6) compared with control (14.4), which correlated with enhanced thrombus formation (mean thrombus size ranged from 1098 to 6476 versus 594 mu m(2) for control).Conclusions-Activation of ECs by aPL antibodies in vivo may create a prothrombotic state on ECs, which may be the first pathophysiological event of thrombosis in APS.