E-Selectin mediates pathogenic effects of antiphospholipid antibodies
E-Selectin mediates pathogenic effects of antiphospholipid antibodies
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DOI：
10.1046/j.1538-7836.2003.00119.x
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发表时间：
2003-04-01
影响因子：
10.4
通讯作者：
Pierangeli, SS
中科院分区：
文献类型：
--
作者：
Espinola, RG;Liu, X;Pierangeli, SS
抗磷脂综合征（APS）患者体内检测到的抗磷脂（aPL）抗体与血栓形成、妊娠丢失和血小板减少症有关。研究表明，aPL在体内具有血栓形成性，但涉及的机制尚未完全了解。几项研究已经证明，aPL抗体在体外和体内激活内皮细胞（EC），如通过上调粘附分子（E-选择素（E-sel）、细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1））所确定的。这些研究的目的是确定aPL抗体对内皮细胞上E-选择素表达的影响，对单核细胞与内皮细胞粘附的影响，以及研究F-选择素对aPL抗体增强体内血栓形成和内皮细胞活化的作用。我们证明，在4小时内，用肿瘤坏死因子-α（TNF-α）处理HUVEC时，ELISA法测定的E-选择素表面表达增加了400倍，用aPL抗体处理时增加了421倍。APL抗体还诱导核因子-κ B（NF-κ B）的活化。与IgG-NHS处理的小鼠相比，APL抗体显著增加了C57 BL/6 J小鼠体内粘附于EC的a白细胞的数量。这种效应在E-选择素缺陷小鼠中被消除。当与用IgG-NHS处理的小鼠相比时，用aPL抗体处理的C57 BL/6 J小鼠中的血栓尺寸显著增加。在用aPL抗体处理的E-选择素缺陷小鼠中，aPL抗体对血栓大小的这种增强被消除。
Antiphospholipid (aPL) antibodies, detected in patients with antiphospholipid syndrome (APS) are associated with thrombosis, pregnancy loss and thrombocytopenia. Studies have shown that aPL are thrombogenic in vivo, but the mechanism(s) involved are not completely understood. Several studies have demonstrated that aPL antibodies activate endothelial cells (ECs) in vitro, as determined by up-regulation of adhesion molecules: E-selectin (E-sel); intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and in vivo. The objectives of these study were to determine the effects of aPL antibodies on the expression of E-selectin on ECs, on the adhesion of monocytes to ECs and to Study the role of F-selectin on aPL antibodies enhanced thrombus formation and activation of ECs in vivo. We demonstrated that the surface expression of E-selectin on HUVEC by ELISA was increased 400-fold when treated with tumor necrosis factor-alpha (TNF-alpha) and 421-fold when treated with aPL antibodies during 4 h. APL antibodies also induced activation of the nuclear factor-kappa B (NF-kappaB). APL antibodies increased significantly the number of adhering a leukocytes to ECs in vivo in C57BL/6 J mice when compared to IgG-NHS treated mice. This effect was abrogated in E-selectin-deficient mice. The thrombus size was significantly increased in C57BL/6 J mice treated with aPL antibodies when compared to mice treated with IgG-NHS. This enhancement in thrombus size by aPL antibodies was abrogated in E-selectin-deficient mice treated with aPL antibodies.