PATTERNS OF INFLAMMATORY VASCULAR ENDOTHELIAL CHANGES IN MURINE LIVER GRAFTS

We have investigated the vascular endothelial phenotypes found at various times posttransplant in murine B10-C3H liver grafts. In this model, liver allografts are spontaneously accepted, and survive indefinitely unless the recipient is first allosensitized with a skin allograft, in which case the liver allografts are rejected within five days. In our previous studies, allograft inflammation was associated with the development of vascular endothelial reactivity with the mAbs MECA-32 and M/K-2 (anti-VCAM-1). We observed that vascular endothelia in both liver isografts and allografts develop reactivity with MECA-32 mAb within two days of transplantation, indicating endothelial activation in both situations. In contrast, only the endothelia in liver allografts develop VCAM-1 expression, as detected with M/K-2 mAb. VCAM-1 was expressed in both rejecting and accepting liver allografts, demonstrating that endothelial VCAM-1 expression is indicative of ongoing graft inflammation but not necessarily graft rejection. Liver parenchymal cells did not appear to develop reactivity with either antibody under any of the conditions tested, In contrast, bile duct epithelia developed M/K-2 reactivity (VCAM-1 expression), but not MECA-32 reactivity in liver allografts, but not isografts. These data demonstrate alloantigen-dependent and alloantigen-independent patterns of endothelial behavior in murine liver grafts that are quite similar to those found in murine cardiac grafts. Further, they demonstrate that the expression of VCAM-1 by graft endothelia is not diagnostic for acute rejection of liver allografts.