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Mucosal Addressin Cell Adhesion Molecule (MAdCAM-1) Expression Is Upregulated in the Cirrhotic Liver and Immunolocalises to the Peribiliary Plexus and Lymphoid Aggregates

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Abstract

Background

Enhanced cell expression of MAdCAM-1 is critical in tissue recruitment of lymphocytes in response to stimuli expressing the α4β7 integrin. MAdCAM-1 is well characterized in gut mucosa with emerging evidence of hepatic expression.

Aims

(i) Compare quantitative/semi-quantitatively MAdCAM-1 expression in relation to early and advanced liver diseases (ii) Define the fine structure of vascular plexuses/lymphatics in the portal tract on which MAdCAM-1 is expressed.

Methods

Using alkaline phosphatase anti-alkaline phosphatase methodology on paraffin embedded tissue sections (n = 28) from cirrhotic individuals who underwent orthotopic liver transplant, we evaluated MAdCAM-1 expression and compared with pre-cirrhotic, fulminant hepatitis B, and non-cirrhotic portal hypertension tissue sections. The positive controls included normal colon tissue with negative controls without primary antibody and isotype-matched purified IgG. We developed a real time PCR to quantify levels of MAdCAM-1 mRNA in our samples.

Results

MAdCAM-1 was expressed in 27/28 of the cirrhotic sections, localized primarily to septal areas within (i) endothelium of the peribiliary vascular plexus (PBP) (ii) lymphoid aggregates, with absence from normal, non-cirrhotic portal hypertension and pre-cirrhotic livers. There was significant upregulation of MAdCAM-1 mRNA in cirrhosis (p < 0.011), consistent with immunohistochemical analysis.

Conclusions

MAdCAM-1 is up-regulated in cirrhosis with expression on PBP and lymphoid aggregates. MAdCAM-1 is likely to contribute to the localization and recruitment of α4β7 lymphocytes during the pathogenesis of cirrhosis. MAdCAM-1 could be a useful marker of advanced liver disease. Further studies with respect to the expression of MAdCAM-1 in the presence of reversible and non-reversible stages of liver disease may be of merit.

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Acknowledgments

A. A. was supported by a Wellcome Trust Training Fellowship, Royal College of Physicians London Sheila Sherlock Hepatology Travelling Fellowship, St Johns Ambulance Trust, Digestive Diseases Foundation/Tana Trust Project grants and the National Institute of Health and Research (NIHR). The work was approved by The Royal Free Hospital Ethics Committee (Ethics ID 5441, Project ID 5441). We are grateful to Dr Kerjaschki, Dept of Clinical Pathology, University of Vienna for the gift of antipodoplanin antibody.

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Authors and Affiliations

  1. Faculty of Health & Medical Sciences and Faculty of Health Care Management & Policy, University of Surrey, Surrey, GU2 7TE, UK

    Aftab Ala

  2. Department of Cellular Pathology, UCL Medical School, Royal Free Campus, London, NW3 2PF, UK

    Korsa Khan, Richard Standish & Amar P. Dhillon

  3. Division of Liver Diseases, Department of Medicine and Recanti/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, Madison Avenue, New York, NY, USA

    Joseph A. Odin & Thomas D. Schiano

  4. Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, Madison Avenue, New York, NY, USA

    M. Isabel Fiel

  5. Institute of Pathology, GeneTech, South San Francisco, San Francisco, CA, USA

    Kenneth J. Hillan

  6. European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, UK

    Syed A. Rahman

  7. Centre for Gastroenterology, Hepatology and Nutrition, Frimley Park Hospital NHS Foundation Trust, Surrey, GU16 7UJ, UK

    Aftab Ala

  8. Institute for Liver & Digestive Health, UCL Medical School, Royal Free Campus, London, NW3 2PF, UK

    David Brown & Humphrey J. F. Hodgson

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  1. Aftab Ala
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  2. David Brown
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Correspondence to Aftab Ala.

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Ala, A., Brown, D., Khan, K. et al. Mucosal Addressin Cell Adhesion Molecule (MAdCAM-1) Expression Is Upregulated in the Cirrhotic Liver and Immunolocalises to the Peribiliary Plexus and Lymphoid Aggregates. Dig Dis Sci 58, 2528–2541 (2013). https://doi.org/10.1007/s10620-013-2755-1

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  • DOI: https://doi.org/10.1007/s10620-013-2755-1

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