Mucosal addressin cell adhesion molecule (MAdCAM-1) expression is upregulated in the cirrhotic liver and immunolocalises to the peribiliary plexus and lymphoid aggregates.

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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