Gomez-Lopez Nardhy, Romero Roberto, Xu Yi, Leng Yaozhu, Garcia-Flores Valeria, Miller Derek, Jacques Suzanne M, Hassan Sonia S, Faro Jonathan, Alsamsam Adham, Alhousseini Ali, Gomez-Roberts Hunter, Panaitescu Bogdan, Yeo Lami, Maymon Eli
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI; Department of Immunology, Microbiology, and Biochemistry, Wayne State University School of Medicine, Detroit, MI.
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI.
Am J Obstet Gynecol. 2017 Dec;217(6):693.e1-693.e16. doi: 10.1016/j.ajog.2017.09.013. Epub 2017 Sep 28.
Neutrophils are the most abundant white blood cells found in the amniotic cavity of women with intraamniotic infection and/or inflammation. The current belief is that these neutrophils are of fetal origin. However, abundant neutrophils have been found in the amniotic fluid of women with a severe acute maternal inflammatory response but without a severe fetal inflammatory response in the placenta, suggesting that these innate immune cells can also be of maternal origin or a mixture of both fetal and maternal neutrophils.
We sought to investigate the origin of amniotic fluid neutrophils from women with intraamniotic infection and/or inflammation and to correlate these findings with acute histologic maternal and fetal inflammatory responses in the placenta.
Amniotic fluid was collected from 15 women with suspected intraamniotic infection and/or inflammation (positive microbiological cultures and/or interleukin-6 concentrations ≥2.6 ng/mL). Amniotic fluid neutrophils were purified by fluorescence-activated cell sorting, DNA was extracted, and DNA fingerprinting was performed. DNA fingerprinting was also performed in the umbilical cord and maternal blood DNA. Fluorescence in situ hybridization was assayed in women with male neonates. Blinded placental histopathological evaluations were conducted.
First, DNA fingerprinting revealed that 43% (6/14) of women who underwent a single amniocentesis had mostly fetal neutrophils in the amniotic fluid. Second, DNA fingerprinting showed that 36% (5/14) of the women who underwent a single amniocentesis had predominantly maternal neutrophils in the amniotic fluid. Third, DNA fingerprinting indicated that 21% (3/14) of the women who underwent a single amniocentesis had an evident mixture of fetal and maternal neutrophils in the amniotic fluid. Fourth, DNA fingerprinting revealed that a woman who underwent 2 amniocenteses (patient 15) had fetal neutrophils first, and as infection progressed, abundant maternal neutrophils invaded the amniotic cavity. Fifth, fluorescence in situ hybridization confirmed DNA fingerprinting results by showing that both fetal and maternal neutrophils were present in the amniotic fluid. Sixth, most of the women who had predominantly amniotic fluid neutrophils of fetal origin at the time of collection delivered extremely preterm neonates (71% [5/7]). Seventh, all of the women who had predominantly amniotic fluid neutrophils of maternal origin at the time of collection delivered term or late preterm neonates (100% [6/6]). Eighth, 2 of the women who had an evident mixture of fetal and maternal neutrophils in the amniotic fluid at the time of collection delivered extremely preterm neonates (67% [2/3]), and the third woman delivered a term neonate (33% [1/3]). Finally, most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (87% [13/15]).
Amniotic fluid neutrophils can be either predominantly of fetal or maternal origin, or a mixture of both fetal and maternal origin, in women with intraamniotic infection and/or inflammation. The findings herein provide evidence that both fetal and maternal neutrophils can invade the amniotic cavity, suggesting that both the fetus and the mother participate in the host defense mechanisms against intraamniotic infection.
中性粒细胞是羊膜腔内感染和/或炎症女性羊水中最丰富的白细胞。目前认为这些中性粒细胞来源于胎儿。然而,在患有严重急性母体炎症反应但胎盘无严重胎儿炎症反应的女性羊水中发现了大量中性粒细胞,这表明这些先天免疫细胞也可能来源于母体,或者是胎儿和母体中性粒细胞的混合。
我们试图研究羊膜腔内感染和/或炎症女性羊水中性粒细胞的来源,并将这些发现与胎盘急性组织学母体和胎儿炎症反应相关联。
从15名疑似羊膜腔内感染和/或炎症(微生物培养阳性和/或白细胞介素-6浓度≥2.6 ng/mL)的女性中收集羊水。通过荧光激活细胞分选纯化羊水中性粒细胞,提取DNA并进行DNA指纹分析。还对脐带和母体血液DNA进行了DNA指纹分析。对男性新生儿的母亲进行荧光原位杂交检测。进行了盲法胎盘组织病理学评估。
首先,DNA指纹分析显示,接受单次羊膜腔穿刺的女性中,43%(6/14)的羊水主要为胎儿中性粒细胞。其次,DNA指纹分析表明,接受单次羊膜腔穿刺的女性中,36%(5/14)的羊水主要为母体中性粒细胞。第三,DNA指纹分析表明,接受单次羊膜腔穿刺的女性中,21%(3/14)的羊水有明显的胎儿和母体中性粒细胞混合。第四,DNA指纹分析显示,接受两次羊膜腔穿刺的一名女性(患者15)首先是胎儿中性粒细胞,随着感染进展,大量母体中性粒细胞侵入羊膜腔。第五,荧光原位杂交通过显示羊水中同时存在胎儿和母体中性粒细胞,证实了DNA指纹分析结果。第六,大多数在采集时羊水主要为胎儿来源中性粒细胞的女性分娩了极早产儿(71%[5/7])。第七,所有在采集时羊水主要为母体来源中性粒细胞的女性分娩了足月儿或晚期早产儿(100%[6/6])。第八,两名在采集时羊水有明显胎儿和母体中性粒细胞混合的女性分娩了极早产儿(67%[2/3]),第三名女性分娩了足月儿(33%[1/3])。最后,本研究中的大多数女性在胎盘中出现了急性母体和胎儿炎症反应(87%[13/15])。
在羊膜腔内感染和/或炎症的女性中,羊水中性粒细胞可以主要来源于胎儿或母体,或者是胎儿和母体来源的混合。本文的研究结果提供了证据,表明胎儿和母体中性粒细胞均可侵入羊膜腔,这表明胎儿和母亲都参与了针对羊膜腔内感染的宿主防御机制。