The effect of macrophage depletion on delayed xenograft rejection: studiesin the guinea pig-to-C6-deficient rat heart transplantation model

The purpose of this study was to investigate the effect of macrophage deple tion, using liposome-encapsulated dichloromethylene diphosphonate (Lip-Cl2M DP). on delayed xenograft rejection (DXR) in the guinea pig-to-C6-deficient rat heart transplantation model. In this model, hyperacute rejection does not occur, but, in untreated recipients, xenografts are still destroyed by DXR within 1-2 days. Graft survival was 68 +/- 8.4 h in splenectomized cont rol rats, 77 +/- 16.3 h with Lip-Cl2MDP alone, 99 +/- 10.4 h with deoxysper guarlin (DSG; P < 0.01 vs. controls), and 127 +/- 19.4 h with Lip-Cl2MDP pl us DSG (P ( 0.01 vs. DSG alone). Treatment with DSG alone or in combination with Lip-Cl2MDP resulted in significant reductions in serum IgM levels at rejection. Immunohistological studies showed that Lip-Cl2M DP alone or in c ombination with DSG reduced infiltration of grafts by both ED1 + and ED2 macrophages. These experiments support the concept that macrophages play an important role in DXR and suggest that strategies targeting macrophages ma y be useful in controlling DXR.