King A E, Kelly R W, Sallenave J-M, Bocking A D, Challis J R G
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Placenta. 2007 Nov-Dec;28(11-12):1099-106. doi: 10.1016/j.placenta.2007.06.002. Epub 2007 Jul 30.
The prevention of uterine infection is critical to appropriate fetal development and term delivery. The innate immune system is one component of the uterine environment and has a role in prevention of uterine infection. Natural antimicrobials are innate immune molecules with anti-bacterial, anti-viral and anti-fungal activity. We discuss two groups of natural antimicrobials in relation to pregnancy: (i) the defensins; and (ii) the whey acidic protein motif containing proteins, secretory leukocyte protease inhibitor (SLPI) and elafin. Human beta-defensins (HBD) 1-3 are expressed by placental and chorion trophoblast, amnion epithelium and decidua in term and preterm pregnancy. Elafin shows a similar pattern of localisation while SLPI is produced only by amnion epithelium and decidua. Evidence suggests that there is aberrant production of some natural antimicrobials in pathologic conditions of pregnancy. In preterm premature rupture of membranes (PPROM) levels of SLPI and elafin are reduced in amniotic fluid and fetal membranes, respectively. Elafin and HBD3 increase in chorioamnionitis and levels of the alpha-defensins, HNP1-3, increase in maternal plasma and amniotic fluid in women affected by microbial invasion of the uterus. In vitro culture studies have suggested a mechanism for increased production of natural antimicrobials in chorioamnionitis. Elafin, SLPI, HBD2 and 3 are all upregulated by inflammatory molecules in cells derived from gestational tissues. In summary, production of natural antimicrobials at key sites within the pregnant uterus suggests an important role in prevention of uterine infection during pregnancy and labour. Aberrant production of these molecules in PPROM and chorioamnionitis suggests that they also have a role in pathologic conditions. In particular, upregulation of these molecules by inflammatory molecules present in chorioamnionitis will ensure a robust response to infection.
预防子宫感染对于胎儿的正常发育和足月分娩至关重要。先天免疫系统是子宫内环境的一个组成部分，在预防子宫感染中发挥作用。天然抗菌物质是具有抗菌、抗病毒和抗真菌活性的先天免疫分子。我们讨论两组与妊娠相关的天然抗菌物质：（i）防御素；（ii）含有乳清酸性蛋白基序的蛋白质、分泌型白细胞蛋白酶抑制剂（SLPI）和弹性蛋白酶。人β-防御素（HBD）1 - 3在足月和早产妊娠时由胎盘和绒毛膜滋养层、羊膜上皮和蜕膜表达。弹性蛋白酶显示出类似的定位模式，而SLPI仅由羊膜上皮和蜕膜产生。有证据表明，在妊娠病理状态下，一些天然抗菌物质的产生会异常。在早产胎膜早破（PPROM）时，羊水中的SLPI水平和胎膜中的弹性蛋白酶水平分别降低。在绒毛膜羊膜炎中弹性蛋白酶和HBD3增加，而在受子宫微生物入侵影响的女性中，α-防御素HNP1 - 3在母体血浆和羊水中的水平增加。体外培养研究提出了绒毛膜羊膜炎中天然抗菌物质产生增加的机制。弹性蛋白酶、SLPI、HBD2和HBD3在来自妊娠组织的细胞中均被炎症分子上调。总之，妊娠子宫关键部位天然抗菌物质的产生表明其在预防妊娠和分娩期间子宫感染中起重要作用。这些分子在PPROM和绒毛膜羊膜炎中的异常产生表明它们在病理状态中也起作用。特别是，绒毛膜羊膜炎中存在的炎症分子对这些分子的上调将确保对感染有强烈反应。
