The effect of macrophage depletion on delayed xenograft rejection: studies in the guinea pig-to-C6-deficient rat heart transplantation model.
The purpose of this study was to investigate the effect of macrophage depletion, using liposome-encapsulated dichloromethylene diphosphonate (Lip-Cl2MDP), 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 control rats, 77 +/- 16.3 h with Lip-Cl2MDP alone, 99 +/- 10.4 h with deoxysperguarlin (DSG; P < 0.01 vs. controls), and 127 +/- 19.4 h with Lip-Cl2MDP plus 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-Cl2MDP alone or in combination with DSG reduced infiltration of grafts by both EDI + and ED2 + macrophages. These experiments support the concept that macrophages play an important role in DXR and suggest that strategies targeting macrophages may be useful in controlling DXR.
Wu
G
G
Department of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Korsgren
O
O
van Rooijen
N
N
Wennberg
L
L
Tibell
A
A
D000818:Animals; D003183:Complement C6 / Q000172:deficiency*; D004164:Diphosphonates / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008697:Methane / Q000494:pharmacology*; D051381:Rats; D011922:Rats, Mutant Strains; D014183:Transplantation, Heterologous / Q000276:immunology*
D003183:Complement C6; D004164:Diphosphonates; D006146:Guanidines; D007166:Immunosuppressive Agents; C118184:LE-Cl2MDP; D008697:Methane; C037258:gusperimus