Complement activation in anti-phospholipid syndrome: A clue for an inflammatory process?
Complement activation in anti-phospholipid syndrome: A clue for an inflammatory process?
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DOI：
10.1016/j.jaut.2007.02.013
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发表时间：
2007-03-01
影响因子：
12.8
通讯作者：
Luigi, Meroni Pier
中科院分区：
文献类型：
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作者：
Cavazzana, Ilaria;Manuela, Nebuloni;Luigi, Meroni Pier
抗磷脂综合征(APS)的定义是在持续存在抗磷脂抗体(APL)的情况下，反复出现动/静脉血栓和/或胎儿丢失。在体内实验模型中，APL的血栓形成活性与促炎内皮细胞表型(增加黏附分子[ADM]表达和白细胞黏附)以及促凝血表型(组织因子[TF]表达)有关。这与APL在体外触发细胞内信号转导以及上调内皮细胞ADM、TF和促炎细胞因子/趋化因子在mRNA和蛋白水平的表达的能力是一致的。在体外单核细胞中也有类似的效果报道。此外，APL还需要激活补体才能在体内模型中显示其血栓形成活性。有趣的是，补体激活阻断和肿瘤坏死因子α中和保护动物免受APL诱导的胎儿损失。总而言之，这些发现支持炎症在APS中的作用，尽管患者没有明显的炎症征象。在2例晚期流产(妊娠20周)的APS患者胎盘中未发现补体C3c和C4d的沉积。需要进一步的研究来调查在动物模型中发现的补体激活和炎症过程是否发生在APS患者身上。(C)2007爱思唯尔有限公司。保留所有权利。
Anti-phospholipid syndrome (APS) is defined by recurrent arterial/venous thrombosis and/or fetal losses in the persistent presence of anti-phospholipid antibodies (aPL). In in vivo experimental models aPL thrombogenic activity is associated with a pro-inflammatory endothelial phenotype (increased adhesion molecule [ADM] expression and leukocyte adhesion) in addition to a pro-coagulant one (tissue factor [TF] expression). This is in line with the in vitro aPL ability to trigger intracellular signalling and to up-regulate ADM, TF and pro-inflammatory cytokine/chemokine expression at the mRNA and protein level in endothelial cells. Comparable effects were also reported in monocytes in vitro. In addition, complement activation is required by aPL to display their thrombogenic activity in in vivo models. Interestingly, complement activation blocking as well as Tumor Necrosis Factor alpha neutralization protect animals from aPL-induced fetal losses. Altogether these findings speak in favour for a role of inflammation in APS in spite of the absence of a clear inflammatory signature in the patients. We could not find any complement (C3c and C4d) deposition in the placentas from 2 late abortions (20 weeks of gestation) in APS women. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are taking place in APS patients. (C) 2007 Elsevier Ltd. All rights reserved.