Proinflammatory chemokines in the intestinal lumen contribute to intestinal dysfunction during endotoxemia.
Proinflammatory chemokines in the intestinal lumen contribute to intestinal dysfunction during endotoxemia.
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DOI：
10.1097/shk.0b013e31823cbff1
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Pritts TA
中科院分区：
文献类型：
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作者：
Sonnier DI;Bailey SR;Schuster RM;Gangidine MM;Lentsch AB;Pritts TA
肠衰竭在感染性休克患者中很常见，肠道功能障碍通常表现为他们危重疾病的原因和后果。大多数研究肠衰竭的发病机制集中在全身方面，但很少有数据检查肠腔中的炎症信号。先前在肠道炎症的体外模型中证实了顶端/管腔趋化因子分泌，我们假设内毒素血症将诱导促炎性趋化因子分泌到肠腔中。此外，我们还研究了这些介质对肠道动力障碍的作用。C57/BL 6雄性小鼠腹腔注射LPS。收集血清、肠组织和肠腔内容物用于细胞因子分析。对于肠蠕动研究，在经口管饲趋化因子后进行转运测定。使用在Transwell培养插入物上生长的Caco-2细胞来检查肠上皮在趋化因子分泌中的作用。单核细胞趋化蛋白1（MCP-1/CCL 2）和巨噬细胞源性趋化因子（MDC/CCL 22）在内毒素血症时分泌到多段肠腔。体外研究表明，肠上皮细胞参与单核细胞趋化蛋白1和MDC的分泌，并表达这些趋化因子的CCR 2和CCR 4受体。肠道转运研究表明，口服灌胃MDC导致肠道运动受损。这项研究表明，肠腔是肠道炎症反应中的一个活跃区室。促炎趋化因子在内毒素血症期间分泌到肠腔中。这些腔内趋化因子导致肠动力障碍，使肠衰竭复杂化。
Intestinal failure is common in patients with septic shock, with dysfunction of the gut often manifesting as both a cause and consequence of their critical illness. Most studies investigating the pathogenesis of intestinal failure focus on the systemic aspect, although few data examine the inflammatory signaling in the intestinal lumen. Having previously demonstrated apical/luminal chemokine secretion in an in vitro model of intestinal inflammation, we hypothesized that endotoxemia would induce secretion of proinflammatory chemokines into the intestinal lumen. In addition, we examined the contribution of these mediators to intestinal dysmotility. C57/BL6 male mice were injected intraperitoneally with LPS. Serum, intestinal tissue, and intestinal luminal contents were harvested for cytokine analysis. For intestinal motility studies, a transit assay was performed after oral gavage of chemokines. Caco-2 cells grown on Transwell culture inserts were used to examine the role of the intestinal epithelium in chemokine secretion. Monocyte chemoattractant protein 1 (MCP-1/CCL2) and macrophage-derived chemokine (MDC/CCL22) were secreted into the lumen of multiple segments of the gut during endotoxemia in mice. In vitro work showed that the intestinal epithelium participates in monocyte chemoattractant protein 1 and MDC secretion and expresses the CCR2 and CCR4 receptors for these chemokines. Intestinal transit studies show that oral gavage of MDC results in impaired gut motility. This study demonstrates that the intestinal lumen is an active compartment in the gut's inflammatory response. Proinflammatory chemokines are secreted into the intestinal lumen during endotoxemia. These intraluminal chemokines contribute to intestinal dysmotility, complicating intestinal failure.