Wu G, Korsgren O, van Rooijen N, Wennberg L, Tibell A
Department of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Xenotransplantation. 1999 Nov;6(4):262-70. doi: 10.1034/j.1399-3089.1999.00031.x.
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.
本研究旨在探讨采用脂质体包裹的二氯亚甲基二膦酸盐（Lip-Cl2MDP）清除巨噬细胞对豚鼠至C6缺陷大鼠心脏移植模型中延迟性异种移植排斥反应（DXR）的影响。在该模型中，不会发生超急性排斥反应，但在未治疗的受体中，异种移植物仍会在1 - 2天内被DXR破坏。脾切除的对照大鼠的移植物存活时间为68±8.4小时，单独使用Lip-Cl2MDP时为77±16.3小时，使用脱氧精胍菌素（DSG；与对照组相比，P < 0.01）时为99±10.4小时，使用Lip-Cl2MDP加DSG时为127±19.4小时（与单独使用DSG相比，P < 0.01）。单独使用DSG或与Lip-Cl2MDP联合治疗均导致排斥反应时血清IgM水平显著降低。免疫组织学研究表明，单独使用Lip-Cl2MDP或与DSG联合使用均可减少EDI +和ED2 +巨噬细胞对移植物的浸润。这些实验支持巨噬细胞在DXR中起重要作用这一概念，并表明针对巨噬细胞的策略可能有助于控制DXR。
