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Article first published online: 10 JAN 2011
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 53, Issue 2, pages 661–672, February 2011
How to Cite
Liaskou, E., Karikoski, M., Reynolds, G. M., Lalor, P. F., Weston, C. J., Pullen, N., Salmi, M., Jalkanen, S. and Adams, D. H. (2011), Regulation of mucosal addressin cell adhesion molecule 1 expression in human and mice by vascular adhesion protein 1 amine oxidase activity . Hepatology, 53: 661–672. doi: 10.1002/hep.24085
The authors are grateful to the sponsors of this work: the Marie Curie Early Training Program, the Wellcome Trust, the Finnish Academy, the Sigrid Juselius Foundation, and the NIHR Biomedical Research Unit in Liver Disease.
Potential conflict of interest: Dr. Pullen owns stock in Pfizer. Dr. Jalkanen owns stock in Biotec Therapies.
fax: 0044 121 415 8701
- Issue published online: 27 JAN 2011
- Article first published online: 10 JAN 2011
- Accepted manuscript online: 19 NOV 2010 12:06PM EST
- Manuscript Accepted: 8 NOV 2010
- Manuscript Received: 31 MAR 2010
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. Conclusion: 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. (HEPATOLOGY 2011;53:661-672)