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- Publisher
- Wiley
- Copyright
- Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
- ISSN
- 0908-665X
- eISSN
- 1399-3089
- DOI
- 10.1034/j.1399-3089.1999.00031.x
- Publisher site
- See Article on Publisher Site
Abstract
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 ED1 + 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.
Journal
Xenotransplantation – Wiley
Published: Dec 1, 1999