Effect of plasma exchange and deoxyspergualin on the survival of guinea pig hearts in macrophage-depleted C6-deficient rats
Aim The present study aimed to evaluate the effect of a combination of plasma exchange (PE) with deoxyspergualin (DSG) on the survival of guinea pig hearts in macrophage-depleted C6-deficient (C6-) rats.
Materials and methods Lip-Cl2MDP (liposome-encapsulated dichloromethylene diphosphonate) was given i.v. at a dose of 10 mg/kg two days before transplantation and every five days until rejection. DSG was given i.v. at a dose of 10 mg/kg per day from day −2 until rejection. PE was performed one day before xenografting. All animals were splenectomized just before heart transplantation. The serum levels of anti-guinea pig IgM and IgG were measured using ELISA.
Results Graft survival was 2.8 ± 0.5 days in control rats, and 4.0 ± 0.3 days with PE alone. A combination of PE with Lip-Cl2MDP or DSG did not improve the results (4.2 ± 0.6 vs. 4.8 ± 0.6 days, respectively), while in rats treated with PE and the combination of Lip-Cl2MDP and DSG, graft survival was significantly prolonged (6.9 ± 1.1 days, P < 0.01 vs. controls). In untreated control rats, xenoreactive IgM and IgG levels decreased immediately after PE, but their levels rapidly returned to normal. In rats treated with DSG or DSG plus Lip-Cl2MDP, the IgM levels remained low during the observation period. Immunohistology showed that macrophage infiltration into the graft was suppressed in Lip-Cl2MDP-treated groups at the time of rejection. T-cell infiltration increased with longer graft survival.
Conclusions Our results demonstrate that sustained suppression of xenoreactive antibodies can be achieved by PE in combination with DSG and xenograft survival is further prolonged in macrophage-depleted C6- rats. These findings suggest that strategies targeting xenoreactive antibodies and macrophages may be useful in prolonging xenograft survival. T-cells seem to be involved in later phase of xenograft rejection.