Effect of cyclosporine on distribution of macrophage subpopulations in rat hepatic allograft.

Macrophage subpopulations infiltrating the grafts of ACI(RT1a) to LEW(RT1(1)) orthotopic rat liver transplants treated with or without immunosuppressive therapy were studied using immunohistochemical staining. LEW recipients of ACI liver transplants experienced severe acute graft rejection, with a mean survival of only 10.2 +/- 0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophage subpopulations infiltrating the grafts, as defined by specific anti-rat macrophage monoclonal antibodies, designated TRPM-1 (pan-macrophage), TRPM-3 (activated macrophage) and Ki-M2R (tissue macrophage). TRPM-1+ or TRPM-3+ cells gradually increased on days 5 and 7 in the untreated hepatic allografts, whereas no significant changes in the number of these cells were observed in the isografts. Treatment with cyclosporine (CsA) greatly decreased the number of these two different types of cells infiltrating the hepatic allografts, compared to the untreated hepatic allografts or the isografts. The time course of the accumulation of these cells in the allografts treated with CsA showed a similar pattern; the cells increased gradually by day 5 and thereafter decreased. This pattern is different from that observed in the untreated allografts or in the isografts. There was no significant difference in the number of Ki-M2R+ cells between the untreated hepatic allografts and the isografts. However, the number of the Ki-M2R+ cells in the hepatic allografts treated with CsA was much less than that of either the untreated allografts or the isografts. These findings suggest that a progressive relative increase in host TRPM-3+ macrophage is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft.2+ allograft, even when compared with the isografts.