Evidence of participation of soluble CD14 in the host response to microbial invasion of the amniotic cavity and intra-amniotic inflammation in term and preterm gestations.
Evidence of participation of soluble CD14 in the host response to microbial invasion of the amniotic cavity and intra-amniotic inflammation in term and preterm gestations.
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DOI：
10.1080/713605697
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发表时间：
2002-11-01
期刊：
影响因子：
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通讯作者：
Yoon, B H
中科院分区：
文献类型：
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作者：
Espinoza, J;Chaiworapongsa, T;Yoon, B H
目的：内毒素与早产感染的发生机制有关。为了发挥其生物学作用，内毒素结合称为脂多糖结合蛋白（LBP）的循环蛋白，并将内毒素单体呈递给CD 14，CD 14可以是膜结合受体或可溶性分子。内毒素-LBP-CD 14复合物与Toll样受体4和其他调节蛋白相互作用，导致细胞活化和炎症反应。本研究的目的是确定是否微生物侵入羊膜腔（MIAC）/羊膜内炎症（早产和足月）和足月分娩与羊水和脐带血浆可溶性CD 14（sCD 14）浓度的变化相关。第1组，胎膜完整的早产伴MIAC/羊膜内炎症组（n = 18）和无MIAC/羊膜内炎症组（n = 26）;第2组，未临产的足月妊娠，无MIAC/羊膜内炎症（n = 11），第3组为在妊娠中期接受遗传性羊膜腔穿刺术的患者（n = 8）。除第3组外，所有患者均在分娩后采集脐带血样本。sCD 14测定采用灵敏度高、特异性强的免疫分析法。非参数统计用于分析。结果：sCD 14在97%（85/88）的羊水标本中可检出。足月患者的羊水sCD 14浓度低于妊娠中期（妊娠中期：中位数482 ng/ml，范围258-838 ng/ml vs.足月无分娩：中位数7 ng/ml，范围2-274 ng/ml，p = 0.01）。在胎膜完整的早产患者中，MIAC/羊膜内炎症患者的中位羊水sCD 14水平高于无这些疾病的患者（分别为中位数1568 ng/ml，范围98-5887 ng/ml vs.中位数645 ng/ml，范围0-3961 ng/ml; p = 0.01）。在足月分娩的妇女中，患有MIAC/羊膜内炎症的妇女的中位羊水sCD 14浓度高于没有这些条件的妇女（中位85 ng/ml，范围2-1113 ng/ml vs.中位17 ng/ml，范围0-186 ng/ml; p = 0.01）。在胎膜完整的早产妇女中，MIAC/羊膜内炎症与较高的脐静脉血浆sCD 14浓度中位数相关（中位数744 ng/ml，范围0-3620 ng/ml vs.中位数0 ng/ml，范围0-2060 ng/ml; p = 0.04）。所有足月妇女所生新生儿的脐带血浆中均未检测到sCD 14。羊水中sCD 14浓度的增加，观察到的情况下，宫内感染，不仅由革兰氏阴性菌，但也革兰氏阳性菌和脲原体属。结论：sCD 14是一种生理成分的羊水，其浓度在足月低于中期妊娠。宫内感染/炎症与早产和足月分娩中较高的羊水sCD 14浓度中位数相关。新生儿出生的母亲早产完整的膜和MIAC/羊膜内炎症有较高的中位浓度的sCD 14在脐带血浆比那些没有这些条件。即使在没有微生物证实的革兰氏阴性感染的情况下，羊水和脐带血中的sCD 14浓度也会增加。即使在涉及生殖器支原体的病例中，CD 14似乎也参与了宫内感染的宿主反应。
OBJECTIVE: Endotoxin has been implicated in the mechanism responsible for the setting of infection in preterm labor. To exert its biological effects, endotoxin binds to a circulating protein known as lipopolysaccharide binding protein (LBP) and presents endotoxin monomers to CD14, which may be a membrane-bound receptor or a soluble molecule. The endotoxin-LBP-CD14 complex interacts with Toll-like receptor 4 and other regulatory proteins leading to cellular activation and an inflammatory response. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC)/intra-amniotic inflammation (both preterm and term) and parturition at term are associated with changes in the amniotic fluid and umbilical plasma soluble concentrations of CD14 (sCD14).STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 88 patients in the following groups: group 1, preterm labor with intact membranes with MIAC/intra-amniotic inflammation (n = 18) and without these conditions (n = 26); group 2, term gestations not in labor without MIAC/intra-amniotic inflammation (n = 11), in labor without MIAC/intra-amniotic inflammation (n = 12) and in labor with MIAC/intra-amniotic inflammation (n = 13); and group 3, patients who underwent genetic amniocentesis at mid-trimester (n = 8). A sample of cord blood was obtained after delivery in all patients except those in group 3. sCD14 was assayed with a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant.RESULTS: sCD14 was detectable in 97% (85/88) of the amniotic fluid samples. Amniotic fluid sCD14 concentrations were lower in patients at term than in the mid-trimester of pregnancy (mid-trimester: median 482 ng/ml, range 258-838 ng/ml vs. term no labor: median 7 ng/ml, range 2-274 ng/ml, p = 0.01). Among patients with preterm labor with intact membranes, the median amniotic fluid sCD14 level of patients with MIAC/intra-amniotic inflammation was higher than in patients without these conditions (median 1568 ng/ml, range 98-5887 ng/ml vs. median 645 ng/ml, range 0-3961 ng/ml, respectively; p = 0.01). Among women at term in labor, those with MIAC/intra-amniotic inflammation had a higher median amniotic fluid sCD14 concentration than those without these conditions (median 85 ng/ml, range 2-1113 ng/ml vs. median 17 ng/ml, range 0-186 ng/ml; p = 0.01). MIAC/intra-amniotic inflammation in women with preterm labor with intact membranes was associated with a higher median umbilical venous plasma sCD14 concentration (median 744 ng/ml, range 0-3620 ng/ml vs. median 0 ng/ml, range 0-2060 ng/ml; p = 0.04). sCD14 was undetectable in plasma from umbilical cords of all neonates born to women at term. An increase in amniotic fluid concentration of sCD14 was observed in cases of intrauterine infection, not only by gram-negative bacteria, but also gram-positive bacteria and Ureaplasma spp.CONCLUSION: sCD14 is a physiological constituent of amniotic fluid, and its concentrations at term are lower than in the mid-trimester. Intrauterine infection/inflammation is associated with a higher median amniotic fluid sCD14 concentration in both preterm and term parturition. Neonates born from mothers with preterm labor with intact membranes and MIAC/intra-amniotic inflammation had a higher median concentration of sCD14 in umbilical cord plasma than those without these conditions. sCD14 concentrations are increased in the amniotic fluid and umbilical cord blood even in the absence of a microbiologically proven gram-negative infection. CD14 appears to participate in the host response to intrauterine infection even in cases involving genital mycoplasmas.