In Situ Macrophage Distribution in the Hepatic Allograft Associated with Rejection in the Rat

Abstract

The association of macrophage infiltration with orthotopic rat liver transplant rejection was studied in the ACI(RT1 a) to the LEW(RT1 1) rat combination, using immunohistochemical staining with several monoclonal antibodies at different time points. LEW recipients of ACI liver transplants experienced severe acute rejection, with a mean survival of 10.2 ± 0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophages infiltrating the grafts as defined by specific rat anti-macrophage monoclonal antibodies designated TRPM-3 and KI-M2R. In addition, the monoclonal antibodies MRC OX3 and MRC OX6 were used to detect the macrophages that expressed Ia antigens. MRC OX3 binds only with the host LEW Ia antigens, but MRC OX6 binds with both host LEW and donor ACI Ia antigens. OX3 + and OX6 + macrophages were seen in the periportal area of the hepatic allograft on Day 5; thereafter, the number of these cells increased in the periportal and pericentral areas as well as in the sinusoidal lumens. A large number of TRPM-3 + cells were also seen at the periportal area in the hepatic allograft on Day 5, whereas there was no increase in the number of KI-M2R + cells. In addition, most of the infiltrating mononuclear cells were OX3 +. These findings suggest that a large number of TRPM-3 + macrophages of recipient origin migrate into the hepatic allograft soon after transplantation. A progressive relative increase in host TRPM-3 + macrophages is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft.