Regulation of mucosal addressin cell adhesion molecule 1 expression in human and mice by vascular adhesion protein 1 amine oxidase activity.
Regulation of mucosal addressin cell adhesion molecule 1 expression in human and mice by vascular adhesion protein 1 amine oxidase activity.
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DOI：
10.1002/hep.24085
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发表时间：
2011-02
期刊：
影响因子：
13.5
通讯作者：
Adams, David H.
中科院分区：
文献类型：
--
作者：
Liaskou, Evaggelia;Karikoski, Marika;Reynolds, Gary M.;Lalor, Patricia F.;Weston, Chris J.;Pullen, Nick;Salmi, Marko;Jalkanen, Sirpa;Adams, David H.
原发性硬化性胆管炎(PSC)和自身免疫性肝炎(AIH)是与炎症性肠病(IBD)相关的肝脏并发症。黏膜寻址细胞黏附分子-1(MAdCAM-1)的表达是IBD发生发展的前提条件，在IBD相关的肝脏疾病中也可检测到MAdCAM-1的表达。肝脏MAdCAM-1的这种异常表达导致最初在肠道激活的效应细胞重新聚集到肝脏，在那里它们导致肝脏损伤。然而，导致MAdCAM-1在肝脏中异常表达的因素尚不清楚。在本研究中，我们发现在肿瘤坏死因子α存在下，血管黏附蛋白-1(一种在人肝中表达的氨基脲敏感的胺氧化酶)对甲胺的脱氨基作用可诱导肝内皮细胞和人完整肝组织中功能性MAdCAM-1的表达。这与PSC患者的淋巴细胞与肝血管的粘附性增加有关。给小鼠喂食甲胺，门静脉血中发现的食物和香烟烟雾的一种成分，导致体内黏膜血管中VAP-1/SSAO依赖的MAdCAM-1表达。食物和香烟烟雾中的一种成分甲胺激活VAP-1/SSAO的酶活性，诱导肝血管MAdCAM-1的表达，从而促进粘膜效应淋巴细胞向肝脏的募集。这可能是IBD肝脏并发症发生的重要机制。
Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are hepatic complications associated with inflammatory bowel disease (IBD). The expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on mucosal endothelium is a prerequisite for the development of IBD and it is also detected on hepatic vessels in liver diseases associated with IBD. This aberrant hepatic expression of MAdCAM-1 results in the recruitment of effector cells initially activated in the gut to the liver where they drive liver injury. However the factors responsible for the aberrant hepatic expression of MAdCAM-1 are not known. In this study we show that deamination of methylamine by vascular adhesion protein-1 (VAP-1) [a semicarbazide sensitive amine oxidase (SSAO) expressed in human liver] in the presence of TNFα, induces expression of functional MAdCAM-1 in hepatic endothelial cells and in intact human liver tissue ex-vivo. This is associated with increased adhesion of lymphocytes from patients with PSC to hepatic vessels. Feeding mice methylamine, a constituent of food and cigarette smoke found in portal blood, led to VAP-1/SSAO-dependent MAdCAM-1 expression in mucosal vessels in-vivo. Activation of VAP-1/SSAO enzymatic activity by methylamine, a constituent of food and cigarette smoke, induces the expression of MAdCAM-1 in hepatic vessels resulting in enhanced recruitment of mucosal effector lymphocytes to the liver. This could be an important mechanism underlying the hepatic complications of IBD.
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