Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset.

Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset.
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狼疮抗凝剂在膜联蛋白 V 结合抗体子集中的细胞凋亡诱导活性的定位。

DOI:
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发表时间:
1998
影响因子:
15.9
通讯作者:
Y. Wada
Y. Wada
中科院分区:
医学1区
文献类型:
--
作者:
N. Nakamura;T. Ban;K. Yamaji;Y. Yoneda;Y. Wada

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狼疮抗凝剂(LAC)与动脉和静脉血栓形成、血小板减少和复发性胎儿丢失有关。我们以前已经报道,具有LAC活性的血浆诱导内皮细胞凋亡并与Annexin V(Nakamura,N.,Y.Shidara,N.Kawaguchi,C.Azuma,N.Mitsuda,S.Onishi,K.Yamaji和Y.Wada)结合。1994年。生物化学。生物群落。[中英文摘要]Re.Commun.205:1488-1493)。在这项研究中,我们从10名LAC患者中分离出两个抗体组份,一个与Annexin V有亲和力,另一个不与Annexin V亲和力。在所有10例患者中,Lac和细胞凋亡活性均定位于Annexin V结合组分。DNA断裂呈剂量依赖关系,与人脐静脉内皮细胞培养液中加入的免疫球蛋白的量平行,并可被膜联蛋白V预先孵育所抑制。用磷脂脂质体从患者的免疫球蛋白中移除抗磷脂抗体并不能取消诱导细胞凋亡的活性或与膜联蛋白V的结合。这些结果表明,LAC患者通常有不结合磷脂的抗体,而是诱导内皮细胞凋亡的抗体。
Lupus anticoagulant (LAC) is associated with arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. We have reported previously that plasma with LAC activity induces apoptosis in endothelial cells and binds annexin V (Nakamura, N., Y. Shidara, N. Kawaguchi, C. Azuma, N. Mitsuda, S. Onishi, K. Yamaji, and Y. Wada. 1994. Biochem. Biophys. Res. Commun. 205:1488-1493). In this study, we separated two IgG antibody fractions, one with and one without affinity for annexin V, from 10 patients with LAC. LAC and apoptotic activities were localized in the annexin V-binding fraction in all 10 patients. DNA fragmentation was dose-dependent, paralleling the amount of IgG added to the human umbilical vein endothelial cell culture medium, and was inhibited by preincubation with annexin V. Removal of the antiphospholipid antibodies from patient IgG with phospholipid liposomes did not abolish the apoptosis-inducing activities or binding to annexin V. These results imply that patients with LAC often have antibodies that do not bind phospholipids and are responsible for the induction of apoptosis in endothelial cells.
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