Heterogeneity of lymphocyte adhesion and extravascular migration in the porto-sinusoidal-hepatic venous system of mice

Lymphocyte infiltration is a main feature of hepatic inflammation. In the p resent study, in order to identify the sites of lymphocyte adhesion and ext ravasation in the porto-sinusoidal-hepatic venous system and the relationsh ip with adhesion molecule expression, we used a mouse model of T cell activ ation-associated hepatitis induced by concanavalin A (Con A). In the sinuso ids and hepatic veins, lymphocytes frequently adhered to the endothelium an d migrated out of the vessels at 8 h alter Con A injection. In the portal v eins lymphocyte adhesion was rarely seen, in spite of large accumulation in the portal tract. Three dimensional reconstruction revealed that sublobula r veins were the main site for lymphocyte adhesion and extravasation at 20 h. As observed by immunohistochemistry, E-selectin was expressed in the sin usoids, small portal veins and sublobular veins at 4 h and 6 h, while it wa s only weakly expressed in large portal veins and hepatic veins. Expression of VCAM similarly peaked at 3 h and 6 h and reduced at 24 h. Pretreatment of mice with anti-VCAM-1 antibody improved the intrahepatic blood flow and concurrently suppressed Coil A-induced liver injury. These results indicate that the main sites where non-specifically activated lymphocytes undergo a dhesion and extravasation in the hepatic vasculature were the sinusoids and sublobular veins, and that E-selectin and VCAM participate to these events .