Antimicrobial host defense in the upper gastrointestinal tract
Antimicrobial host defense in the upper gastrointestinal tract
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DOI：
10.1097/meg.0b013e3283052ddb
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发表时间：
2008-12-01
影响因子：
2.1
通讯作者：
Wehkamp, Jan
中科院分区：
文献类型：
--
作者：
Hosaka, Yoshio;Koslowski, Maureen;Wehkamp, Jan
背景 除真菌外，食道中的微生物感染很少见。在此，我们的目的是系统地评估不同抗菌宿主因子的分布和数量，以及首次评估上胃肠道的功能性粘膜抗菌活性。方法我们对总共 12 名个体的健康食道、胃和十二指肠的三个不同位置进行了活检。使用实时 PCR 和外部标准，我们比较了编码抗菌肽（包括防御素、抗菌素、杀菌/通透性增加蛋白、牛皮癣素和弹性蛋白）的 mRNA 的绝对表达。此外，我们还对人 β 防御素 1 (HBD1)、elafin 和银屑病素进行了免疫染色。为了测试功能相关性，我们评估了活检中的阳离子提取物对大肠杆菌 ATCC 25922 和白色念珠菌临床分离株的抗菌和抗真菌活性。 结果 与在所有组织中表达相似的 HBD1 相比，健康食道中的诱导型 β-防御素比胃和十二指肠中高得多（对于 HBD2-4：P < 0.01）。此外，抗蛋白酶elafin和银屑病素也主要在食道中表达（P < 0.005）。相反，LL-37 和杀菌/通透性增加蛋白仅少量表达。来自食道和胃的阳离子组织提取物对大肠杆菌表现出有效的抗菌活性。与念珠菌感染的易感性一致，食管提取物对白色念珠菌的活性较弱（P = 0.026）。结论尽管抗菌宿主肽的表达占主导地位，但食管组织对白色念珠菌的杀灭能力较弱。这些数据表明尚不清楚的抗菌分子的重要作用。 Eur J Gastroenterol Hepatol 20:1151-1158 (C) 2008 Wolters Kluwer Health |利平科特·威廉姆斯和威尔金斯。
Background With the exception of fungi, microbial infections are rare in the oesophagus. Herein, we aimed to systematically assess the distribution and quantity of different antimicrobial host factors as well as, for the first time, functional mucosal antimicrobial activity in the upper gastrointestinal tract.Methods We investigated biopsies from the healthy oesophagus, three different locations in the stomach and the duodenum in a total of 12 individuals. Using real-time PCR with external standards, we compared absolute expression of mRNA encoding antimicrobial peptides including defensins, cathelicidin, bactericidal/permeability-increasing protein, psoriasin, and elafin. In addition, we performed immunostaining for human-beta-defensin-1 (HBD1), elafin, and psoriasin. To test functional relevance, we assessed antimicrobial as well as antifungal activity of cationic extracts from biopsies against E coli ATCC 25922 and a clinical isolate of Candida albicans.Results In contrast to HBD1 which was similarly expressed in all tissues, inducible beta-defensins in the healthy oesophagus were much higher compared with the stomach and duodenum (for HBD2-4: P < 0.01). In addition, the antiproteases elafin and psoriasin were also predominantly expressed in the oesophagus (P < 0.005). In contrast LL-37 and bactericidal/permeability-increasing protein were only marginally expressed. Cationic tissue extracts from both the oesophagus as well as the stomach showed potent antibacterial activity against E. coli. Consistent with susceptibility to Candida infection, the esophageal extracts exhibited a weaker activity against C. albicans (P = 0.026).Conclusion Despite dominant expression of antimicrobial host peptides, oesophageal tissue shows a weakened potency to kill C albicans. These data suggest an important role of yet unknown antimicrobial molecules. Eur J Gastroenterol Hepatol 20:1151-1158 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.