Complement activation and regulation in preeclamptic placenta.
Complement activation and regulation in preeclamptic placenta.
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DOI：
10.3389/fimmu.2014.00312
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发表时间：
2014
影响因子：
7.3
通讯作者：
Meri S
中科院分区：
文献类型：
--
作者：
Lokki AI;Heikkinen-Eloranta J;Jarva H;Saisto T;Lokki ML;Laivuori H;Meri S
子痫前期(PE)是一种起源于胎盘的常见妊娠疾病。我们研究了母胎界面补体系统的过度激活或调节不良是否会导致PE的发生。分析补体成分和调节因子在胎盘中的位置和存在情况。对7例早发性PE(妊娠34 周)、5例晚发性PE、10例对照妊娠的胎盘进行冰冻切片，免疫组织化学染色6种补体激活物和6种抑制物。对PE胎盘和对照胎盘进行荧光定量比较。用定量聚合酶链式反应方法检测补体成分C4a和C4b的基因拷贝数。母亲C4缺乏(≥1缺失或无功能C4)在早发性PE组中最常见(71%)，而在晚发性PE组中更常见(60%对38%)。补体C1q沉积在对照组和患者组之间有显著差异：对照组和早发性PE患者的C1q高于晚发性PE患者(平均分别为p = 0.01和p = 0.005)。C3b/iC3b和C3d染色分析C3活化情况。C3d主要定位于基底合胞体，C3b/iC3b弥散分布于其他结构，但两组间无明显差异。合体滋养层细胞中大量观察到活化的C4和膜结合调节因子CD55、CD46和CD59。合胞体结节是富含PE的结构，专用于经典途径抑制物C4BP的染色，而关键调节因子H(FH)在胎盘中分布更广。晚发和早发PE组之间C1q沉积的差异可能预示着这些患者PE症状的不同病因。补体调节因子C4BP和FH在PE胎盘中的不规则分布，以及C4a缺乏的频率较高，表明PE中补体激活和调节之间的平衡失调。
Preeclampsia (PE) is a common disorder of pregnancy originating in the placenta. We examined whether excessive activation or poor regulation of the complement system at the maternal–fetal interface could contribute to the development of PE. Location and occurrence of complement components and regulators in placentae were analyzed. Cryostat sections of placentae were processed from 7 early-onset PE (diagnosis <34 weeks of gestation), 5 late-onset PE, 10 control pregnancies, and immunostained for 6 complement activators and 6 inhibitors. Fluorescence was quantified and compared between PE and control placentae. Gene copy numbers of complement components C4A and C4B were assessed by a quantitative PCR method. Maternal C4 deficiencies (≥1 missing or non-functional C4) were most common in the early-onset PE group (71%), and more frequent in late-onset PE compared to healthy controls (60 vs. 38%). Complement C1q deposition differed significantly between control and patient groups: controls and early-onset PE patients had more C1q than late-onset PE patients (mean p = 0.01 and p = 0.005, respectively). C3 activation was analyzed by staining for C3b/iC3b and C3d. C3d was mostly specific to the basal syncytium and C3b/iC3b diffuse in other structures, but there were no clear differences between the study groups. Activated C4 and membrane-bound regulators CD55, CD46, and CD59 were observed abundantly in the syncytiotrophoblast. Syncytial knots, structures enriched in PE, stained specifically for the classical pathway inhibitor C4bp, whereas the key regulator alternative pathway, factor H (FH) showed a wider distribution in the placenta. Differences in C1q deposition between late- and early-onset PE groups may be indicative of the different etiology of PE symptoms in these patients. Irregular distribution of the complement regulators C4bp and FH in the PE placenta and a higher frequency of C4A deficiencies suggest a disturbed balance between complement activation and regulation in PE.