Weiler Hartmut
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, USA.
J Clin Invest. 2008 Oct;118(10):3276-8. doi: 10.1172/JCI37243.
Fetal loss induced by antiphospholipid antibodies (aPLs) in mice is a complement-driven inflammatory condition. Engagement of the complement receptor C5aR on neutrophils induces expression of the principal initiator of the blood clotting mechanism, tissue factor (TF), and blocking this downstream event of complement activation prevents antibody-induced fetal loss. In this issue of the JCI, the study by Redecha et al. clarifies that in mice, the contribution of TF to this pathogenic mechanism is independent of its role in coagulation and thrombosis, but involves inflammatory signaling through the receptor PAR2 (see the related article beginning on page 3453). The study not only sheds light on a critical effector mechanism of aPL-induced fetal loss, but also suggests that treatment with statins, which decrease TF and PAR2 expression, may hold promise as a therapeutic approach to antiphospholipid syndrome-associated pregnancy complications.
抗磷脂抗体（aPLs）诱导的小鼠胎儿丢失是一种补体驱动的炎症状态。中性粒细胞上补体受体C5aR的激活会诱导凝血机制的主要启动因子组织因子（TF）的表达，而阻断补体激活的这一下游事件可防止抗体诱导的胎儿丢失。在本期《临床研究杂志》中，Redecha等人的研究阐明，在小鼠中，TF对这一致病机制的作用与其在凝血和血栓形成中的作用无关，而是涉及通过受体PAR2的炎症信号传导（见第3453页开始的相关文章）。该研究不仅揭示了aPL诱导胎儿丢失的关键效应机制，还表明他汀类药物治疗可降低TF和PAR2的表达，有望成为治疗抗磷脂综合征相关妊娠并发症的一种方法。
