title: Regulation of mucosal addressin cell adhesion molecule 1 expression in human and mice by vascular adhesion protein 1 amine oxidase activity.
abstract: Primary sclerosing cholangitis (PSC) and autoimmune hepatitis 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 the hepatic vessels of patients with 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, in which 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 (MA) by vascular adhesion protein 1 (VAP-1) [a semicarbazide-sensitive amine oxidase (SSAO) expressed in the human liver] in the presence of tumor necrosis factor α induces the 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 MA, 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.
  
  
  CONCLUSIONS
  Activation of VAP-1/SSAO enzymatic activity by MA, a constituent of food and cigarette smoke, induces the expression of MAdCAM-1 in hepatic vessels and results in the enhanced recruitment of mucosal effector lymphocytes to the liver. This could be an important mechanism underlying the hepatic complications of IBD.
authors.affiliation: Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Liaskou
authors.forename: Marika
authors.initials: M
authors.lastname: Karikoski
authors.forename: Gary M
authors.initials: GM
authors.lastname: Reynolds
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Lalor
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Weston
authors.forename: Nick
authors.initials: N
authors.lastname: Pullen
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D015209:Cholangitis, Sclerosing / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D023421:Models, Animal; D009088:Mucoproteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D008744:Methylamines; D009088:Mucoproteins; D014409:Tumor Necrosis Factor-alpha; C027451:methylamine; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse