title: Mucosal addressin cell adhesion molecule (MAdCAM-1) expression is upregulated in the cirrhotic liver and immunolocalises to the peribiliary plexus and lymphoid aggregates.
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.
  
  
  OBJECTIVE
  (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.
authors.affiliation: Faculty of Health & Medical Sciences, University of Surrey, Surrey, GU2 7TE, UK. aftab.ala@fph-tr.nhs.uk
authors.forename: Aftab
authors.initials: A
authors.lastname: Ala
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Korsa
authors.initials: K
authors.lastname: Khan
authors.forename: Richard
authors.initials: R
authors.lastname: Standish
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Odin
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Fiel
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Schiano
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Hillan
authors.forename: Syed A
authors.initials: SA
authors.lastname: Rahman
authors.forename: Humphrey J F
authors.initials: HJ
authors.lastname: Hodgson
authors.forename: Amar P
authors.initials: AP
authors.lastname: Dhillon
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules; D003106:Colon / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000378:metabolism; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D012333:RNA, Messenger