Figure 4.

Therapeutic manipulation of adhesion molecules in primary sclerosing cholangitis (PSC). In PSC, hepatic vascular adhesion protein 1 (VAP-1) expression is upregulated and its inherent enzymatic properties enable the generation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on liver sinusoidal endothelium. Hepatic CCL25 expression is also upregulated in the PSC liver, although the reasons for this are unclear. The end result is that lymphocytes that have been generated to recognize gut antigens in the setting of inflammatory bowel disease are now misdirected to the liver where they contribute to inflammation and biliary destruction. There are now several available agents targeting these adhesion molecule and chemokine interactions which may represent viable therapeutic options for investigation in PSC.