Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia
Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia
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DOI：
10.1016/j.humimm.2005.11.003
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发表时间：
2005-11-01
期刊：
影响因子：
2.7
通讯作者：
Hahn, S
中科院分区：
文献类型：
--
作者：
Gupta, AK;Hasler, P;Hahn, S
先兆子痫是一种严重的妊娠相关疾病，涉及母体先天免疫系统的明显激活，被认为是由炎症性合胞滋养层微粒（STBM）和细胞因子从潜在的胎盘异常（涉及异常滋养层分化）的释放增加引起的。循环中性粒细胞的激活最近已显示导致含有DNA的纤维细胞外晶格的产生，称为NETs（中性粒细胞细胞外陷阱）。因此，我们研究了胎盘衍生因子是否激活外周中性粒细胞产生NETs，以及在先兆子痫胎盘中NETs的形成是否增加。通过使用流式细胞术测量CD 11b表达来评估胎盘衍生因子（白细胞介素-8和STBM）处理后分离的循环中性粒细胞的活化。此外，NET生成这些激活的中性粒细胞在体外和体内的胎盘组织切片进行了检查，使用电子显微镜和荧光显微镜。我们报告说，胎盘来源的白细胞介素-8和STBM有效地激活中性粒细胞，并触发NET的形成。大量的NET直接存在于先兆子痫胎盘的绒毛间隙中。因此，NET似乎是中性粒细胞活化的一个组成部分，并且它们在先兆子痫中的存在增加表明NET可能在潜在的病理学中起作用。
Preeclampsia, a severe pregnancy-related disorder, involves an overt activation of the maternal innate immune system, proposed to result from the elevated release of inflammatory syncytiotrophoblast microparticles (STBM) and cytokines from underlying placental anomaly involving abnormal trophoblast differentiation. Activation of circulating neutrophils has recently been shown to lead to the generation of fibrous extracellular lattices containing DNA, termed NETs (neutrophil extracellular traps). Therefore, we examined whether placentally derived factors activated peripheral neutrophils to generate NETs, and whether NETs formation was increased in preeclamptic placenta. Activation of isolated circulatory neutrophils on treatment with placentally derived factors (interleukin-8 and STBM) was assessed by measuring CD11b expression using Flow cytometry. Furthermore, NETs generation by these activated neutrophils in vitro and in vivo in the placental tissue sections were examined using electron microscopy and fluorescence microscopy. We report that placentally-derived interleukin-8 and STBM efficiently activated neutrophils and triggered NETs formation. Large numbers of NETs were present directly in the intervillous space of preeclamptic placentae. NETs, therefore, appear to be an integral part of neutrophil activation, and their increased presence in preeclampsia suggests that NETs may play a role in the underlying pathology.