Introduction:

Macrophages are a well-recognized cells of the cellular infiltrate within allograft rejection, but their role has not yet been fully addressed. This study was aimed to examine the effect of macrophage depletion on skin allograft rejection.

Materials and Methods:

Macrophages were depleted in recipient mice by injection of clodronate liposomes before and after skin transplantation till the day of rejection. Skin allograft rejection in C57BL/6 and CD8 knockout (KO) mice across full or class II major histocompatibility complex (MHC) antigens or multiple minor mismatches was compared.

Results:

In fully MHC-mismatched grafts, clodronate liposomes treatment prolonged BALB/c skin graft survival to 12.0±0.3 days in C57BL/6 mice (p=0.0351) and to 14.0±0.3 days in CD8 KO mice (p=0.0007) versus untreated control. In multiple minor mismatched BALB/B skin grafts, clodronate liposomes treatment prolonged graft survival to 13.2±0.4 days in C57BL/6 mice (p=0.0055) and to 14.4±0.4 days in CD8 KO mice (p=0.0042). However, clodronate liposomes treatment did not improve class II mismatched bm12 skin grafts survival time either in C57BL/6 or CD8 KO mice Macrophages in rejecting grafts were markedly reduced in clodronate liposomes-treated mice in comparison with control.

Conclusion:

Clodronate liposomes prolonged skin allograft survival. Hence, macrophages may play an important but not essential role in skin allograft rejection.

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