Induction of vascular adhesion protein-1 during liver allograft rejection and concomitant cytomegalovirus infection in rats

Vascular adhesion protein-1 (VAP-1) is an adhesion molecule controlling lym phocyte recirculation through high endothelial venules of the lymph nodes. It has also been shown to be induced and to mediate lymphocyte adhesion at sites of inflammation. We studied the expression of VAP-1 and two other ind ucible adhesion molecules ICAM-1 and VCAM-1 in our experimental model of ra t liver allograft rejection and, in addition, the effect of concomitant rat cytomegalovirus (RCMV) infection on this expression. Expression of VAP-1, ICAM-1, and VCAM-1 was studied in rat liver allografts with or without RCMV infection, isografts, and normal rat liver. Immunoperoxidase technique and monoclonal antibodies including a novel anti-VAP-1 reagent were used. VAP- 1 expression was induced by acute rejection in sinusoids, hepatocytes, and also in bile ducts,when compared to the isografts or normal liver, where on ly blood vessels were consistently positive. Sinusoidal and hepatocyte expr ession of VAP-1 was prolonged by the presence of RCMV. ICAM-1 and VCAM-1 ex pression was also induced by acute rejection. However, RCMV increased sinus oidal VCAM-1 expression compared to uninfected grafts. The present experime ntal study shows that VAP-1 is up-regulated in acute rejection of liver all ografts, and that this up-regulation is prolonged by RCMV infection.