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INTERVENTION OF AUTOANTIBODY IN THE MEMBRANE PHOSPHOLIPID FLIP-FLOP OF TROPHOBLAST CELLS.

自身抗体对滋养层细胞膜磷脂触发器的干预。

基本信息

批准号：
13670239
负责人：
WADA Yoshinao
金额：
$ 1.6万
依托单位：
RESEARCH INSTITUTE, OSAKAMEDICAL CENTER FOR MATERNAL AND CHILD HEALTH
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Antiphospholipid antibody is an autoantibody associated with antiphospholipid syndrome (APS) representing arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. The underlying mechanism of these complications is not fully understood, while they are obviously due to accelerated coagulation. Since a negatively charged phospholipid, phosphatidylserine, which potentially triggers blood coagulation, is exposed to the outer leaflet of plasma membrane during apoptosis and trophoblast differentiation, we focused on the proteins binding to negatively charged phospholipids in order to delineate the pathogenesis of APS. An affinity column, in which cardiolipin or phosphatidylserine was embedded in octyl cellulose was prepared, and the plasma proteins bound to these phospholipids were collected by elution with 2M NaCl. A proteins were separated by iD or 2D electrophoresis, and then identified by peptide mass fingerprinting. The proteins included beta2 glycoprotein I, inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), complement factor 4, factor H and factor H-related protein I. The binding of factor H was interesting, since factor H mutations cause hemolytic uremic syndrome with characteristic pathology of renal microvascular thrombosis, which also occurs in APS. Recently, the crucial role of alternative complement pathway activation has been reported. Thus, possible involvement of factor H, a regulatory protein of alternative pathway, would be an attractive speculation to delineate the pathogenesis of APS.

抗磷脂抗体是一种与抗磷脂综合征（APS）相关的自身抗体，表现为动脉和静脉血栓形成、血小板减少和复发性流产。这些并发症的潜在机制尚不完全清楚，但它们显然是由于加速凝血。由于带负电荷的磷脂，磷脂酰丝氨酸，这可能会触发血液凝固，暴露于细胞凋亡和滋养层分化过程中的质膜外叶，我们专注于蛋白结合带负电荷的磷脂，以描绘APS的发病机制。制备了将心磷脂或磷脂酰丝氨酸包埋在辛基纤维素中的亲和柱，并通过用2M NaCl洗脱收集与这些磷脂结合的血浆蛋白。通过iD或2D电泳分离A蛋白，然后通过肽质量指纹图谱鉴定。这些蛋白质包括β 2糖蛋白I、α胰蛋白酶抑制剂家族间重链相关蛋白（IHRP）、补体因子4、H因子和H因子相关蛋白I。H因子的结合很有趣，因为H因子突变会导致溶血性尿毒综合征，伴有肾微血管血栓形成的特征性病理，这也发生在APS中。最近，已报道了补体旁路途径激活的关键作用。因此，作为旁路途径的调节蛋白，H因子可能参与APS的发病机制是一个有吸引力的推测。