Chen Q, Stone P R, Woon S-T, Ching L-M, Hung S, McCowan L M E, Chamley L W
Department of Obstetrics & Gynecology, Faculty of Medical & Health Science, The University of Auckland Auckland, New Zealand.
Thromb Res. 2004;114(2):101-11. doi: 10.1016/j.thromres.2004.04.013.
Antiphospholipid antibodies (aPL) cause thrombotic disease and recurrent pregnancy loss. Despite their name it is now clear that the antigen for most antiphospholipid antibodies is the phospholipid-binding protein beta(2) glycoprotein I (beta(2)GPI). However, beta(2) glycoprotein I is only antigenic for antiphospholipid antibodies when the protein is immobilised on a suitable surface such as phosphatidyl serine. It has been suggested that antiphospholipid antibodies bind to beta(2) glycoprotein I on the surface of resting endothelial cells and this in turn leads to endothelial activation and the initiation of thrombosis. However, as phosphatidyl serine is absent from resting endothelial cell membranes, we questioned this hypothesis.
The ability of human antiphospholipid antibody-containing sera and monoclonal antiphospholipid antibodies to interact with endothelial cells was examined using cell-based ELISAs employing human umbilical vein endothelial cells (HUVECs) as the antigen. The expression of adhesion molecules in response to treatment with antiphospholipid antibodies was also measured by a cell-based ELISA. Activation of NF kappa beta was examined using electrophoretic mobility shift assays (EMSAs).
Neither monoclonal antiphospholipid antibodies nor human sera containing antiphospholipid antibodies bound to resting endothelial cells. In contrast, one monoclonal antiphospholipid antibody did bind to both activated and apoptotic endothelial cells.
Antiphospholipid antibodies do not bind to resting endothelial cells nor do antiphospholipid antibodies activate resting endothelial cells. Rather, an independent triggering event is required to activate endothelial cells and subsequently some antiphospholipid antibodies may then bind to the activated endothelial cells and initiate a thrombogenic process.
抗磷脂抗体（aPL）可导致血栓形成性疾病和复发性流产。尽管它们被称为抗磷脂抗体，但现在很清楚，大多数抗磷脂抗体的抗原是磷脂结合蛋白β2糖蛋白I（β2GPI）。然而，只有当该蛋白固定在合适的表面（如磷脂酰丝氨酸）上时，β2糖蛋白I才对抗磷脂抗体具有抗原性。有人提出抗磷脂抗体与静息内皮细胞表面的β2糖蛋白I结合，进而导致内皮细胞活化和血栓形成的起始。然而，由于静息内皮细胞膜中不存在磷脂酰丝氨酸，我们对这一假设提出了质疑。
使用以人脐静脉内皮细胞（HUVECs）为抗原的细胞酶联免疫吸附测定（ELISA），检测含人抗磷脂抗体的血清和单克隆抗磷脂抗体与内皮细胞相互作用的能力。还通过细胞ELISA测量了抗磷脂抗体处理后黏附分子的表达。使用电泳迁移率变动分析（EMSA）检测核因子κB的活化。
单克隆抗磷脂抗体和含抗磷脂抗体的人血清均不与静息内皮细胞结合。相反，一种单克隆抗磷脂抗体确实与活化的和凋亡的内皮细胞结合。
抗磷脂抗体不与静息内皮细胞结合，也不激活静息内皮细胞。相反，需要一个独立的触发事件来激活内皮细胞，随后一些抗磷脂抗体可能会与活化的内皮细胞结合并启动血栓形成过程。
