Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion
Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion
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DOI：
10.1016/j.amjhyper.2004.10.002
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发表时间：
2005-03-01
影响因子：
3.2
通讯作者：
Kellems, RE
中科院分区：
文献类型：
--
作者：
Bobst, SM;Day, MC;Kellems, RE
背景：子痫前期影响3-5%的妊娠。它是孕产妇和胎儿发病和死亡的主要原因。最近的研究表明，抗血管紧张素II型1 （AT,）受体的自身抗体存在于子痫前期患者的血清中。在这项研究中，我们研究了受体激动性自身抗体AT （AT1-AA）在人系膜细胞中对白细胞介素-6 （IL-6）和纤溶酶原激活物抑制剂-1 （Pai-1）分泌的作用。方法：10例重度子痫前期孕妇5例，血压正常孕妇5例。从每个个体中纯化免疫球蛋白g （IgG）。AT1-AA的存在是根据其刺激大鼠新生儿心肌细胞收缩率增加的能力来确定的。选择原代人系膜细胞研究igg诱导IL-6和Pai-1的分泌。使用氯沙坦和表位肽来确定AT1-AA与AT受体的相互作用是否与刺激IL-6和Pai-1分泌有关，并通过AT受体激活介导。结果：子痫前期患者IgG刺激大鼠新生儿心肌细胞收缩率升高。子痫前期患者IgG诱导人系膜细胞AT、受体特异性IL-6和Pai-1的分泌水平显著高于正常血压患者IgG。与表位肽的竞争表明AT1-AA刺激了AT受体。结论：我们的研究结果表明，具有激活AT受体能力的母体自身抗体可能是子痫前期患者肾脏损害的原因。(c) 2005年中国高血压杂志
Background: Preeclampsia affects 3-5% of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Recent studies demonstrate that autoantibodies against the angiotensin II type 1 (AT,) receptor are present in the serum of preeclamptic patients. In this study, we investigated the role of AT, receptor-agonistic autoantibody (AT1-AA) regarding interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (Pai-1) secretion in human mesangial cells.Methods: The study included ten patients: five severely preeclamptic and five normotensive pregnant women. Immunoglobulin-G (IgG) was purified from each individual. The presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of rat neonatal cardiomyocytes. Primary human mesangial cells were chosen to study IgG-induced secretion of IL-6 and Pai-1. Losartan and epitope peptides were used to determine whether AT1-AA interaction with AT, receptor was associated with stimulation of IL-6 and Pai-1 secretion and was mediated through AT, receptor activation.Results: The IgG from preeclamptic patients stimulated an increased contraction rate in rat neonatal cardiomyocytes. The IgG from preeclamptic patients induced the AT, receptor-specific secretion of IL-6 and Pai-1 from human mesangial cells at a significantly higher level than that achieved with IgG from normotensive patients. Competition with an epitope peptide suggested that the AT, receptor was stimulated by AT1-AA.Conclusions: Our findings suggest that a maternal autoantibody with the ability to activate AT, receptors may account for the development of renal damage seen in preeclamptic patients. (c) 2005 American Journal of Hypertension, Ltd.