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首页> 外文期刊>Journal of Pediatric Surgery: Official Journal of the Surgical Section of the American Academy of Pediatric, the British Association of Paediatric Surgeons, the American Pediatric Surgical Association, and the Canadian Association of Paediatric Surgeons >Meconium stimulates a pro-inflammatory response in peritoneal macrophages: implications for meconium peritonitis.
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Meconium stimulates a pro-inflammatory response in peritoneal macrophages: implications for meconium peritonitis.

机译：胎粪刺激腹膜巨噬细胞的促炎反应：对胎粪腹膜炎的影响。

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BACKGROUND/PURPOSE: Although meconium peritonitis is a rare condition, the mortality rate can be as high as 40%. Meconium peritonitis is a result of intestinal perforation in utero, which leads to dense inflammation in the peritoneal cavity. The fetus has relatively immature peritoneal defense mechanisms, so the cause of this dense inflammation is unclear. The peritoneal macrophage is a key cell in the peritoneal inflammatory response in adults. The purpose of this investigation was to determine if sterile meconium had a direct stimulatory effect on the peritoneal macrophage. METHODS: Peritoneal macrophages were harvested from adult C3H/HEN mice. The cells were placed in microtiter wells at 10(5) cells per well. Sterile human meconium was diluted in media and placed in the wells at varying concentrations for 8 hours. Lipopolysaccharide (LPS) (10 microg/mL) served as a positive control. Supernatants were harvested and assayed for tumor necrosis factor alpha (TNF-alpha) using a commercial ELISA kit. Separate cells were assayed for TNF-alpha message using polymerase chain reaction (PCR). In another series of experiments, procoagulant activity (PCA) was determined on freeze-thawed cells using a two-stage amidolytic assay. To test for the role of protein kinase C (PKC) in the PCA response H7, a PKC inhibitor, was used as well. RESULTS: Meconium stimulation resulted in a significant increase in TNF-alpha compared with negative controls with a peak at 0.1% meconium (121 pg/mL v 11 pg/mL, P<.05). There was a significant increase in PCA, with a 10-fold increase with 1% meconium compared with controls (P<.05). This response was limited to less than 5% by PKC inhibition. CONCLUSIONS: Sterile meconium results in a marked proinflammatory response in the peritoneal macrophage with elevations of both PCA and TNF-alpha. The TNF response is likely mediated at a pretranscriptional level because there is a marked increase in TNF mRNA. These data suggest that the PCA response is regulated by a PKC mechanism similar to LPS. Stimulation of the peritoneal macrophage by meconium is a possible cause of the marked inflammation seen in meconium peritonitis.
机译：背景/目的：尽管胎粪腹膜炎是一种罕见的疾病，但其死亡率可能高达40％。胎粪腹膜炎是子宫内子宫穿孔的结果，导致腹膜腔内密集的炎症。胎儿具有相对不成熟的腹膜防御机制，因此尚不清楚这种致密炎症的原因。腹膜巨噬细胞是成年人腹膜炎症反应中的关键细胞。这项研究的目的是确定无菌胎粪是否对腹膜巨噬细胞具有直接的刺激作用。方法：从成年C3H / HEN小鼠中收获腹膜巨噬细胞。将细胞以每孔10（5）个细胞的形式置于微量滴定孔中。将无菌的人胎粪在培养基中稀释，并以不同的浓度放入孔中8小时。脂多糖（LPS）（10微克/毫升）作为阳性对照。收获上清液，并使用市售ELISA试剂盒分析肿瘤坏死因子α（TNF-alpha）。使用聚合酶链反应（PCR）分析单独的细胞中的TNF-α信息。在另一系列实验中，使用两步酰胺水解测定法测定了冻融细胞的促凝活性（PCA）。为了测试蛋白激酶C（PKC）在PCA应答中的作用，还使用了PKC抑制剂H7。结果：与阴性对照相比，胎粪刺激导致TNF-α的显着增加，胎粪的峰值为0.1％（121 pg / mL对11 pg / mL，P <.05）。 PCA显着增加，与对照组相比，胎粪含量为1％时PCA增加了10倍（P <.05）。通过PKC抑制，该应答被限制为小于5％。结论：无菌胎粪会引起腹膜巨噬细胞明显的促炎反应，同时PCA和TNF-α均升高。 TNF反应可能在转录前水平介导，因为TNF mRNA显着增加。这些数据表明，PCA反应受类似于LPS的PKC机制调节。胎粪刺激腹膜巨噬细胞可能是导致胎粪腹膜炎明显炎症的原因。

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