Contribution of activated macrophages to the process of delayed xenograft rejection

Transplantation
Y LinM Waer

Abstract

When hyperacute rejection, involving natural xenoreactive antibodies (XAb) and/or complement (C), can be prevented, xenografts (Xgs) undergo delayed xenograft rejection associated with a progressive mononuclear cell infiltration. We have previously shown that XAb formation can be totally suppressed in leflunomide (LF)-treated, T-deficient nude rats receiving hamster hearts. Hence, this model was well-suited to study a role played by other factors, e.g., natural killer (NK) cells and macrophages (Mphi). The relative contribution of Mphi to delayed xenograft rejection was investigated. In addition to LF (20 mg/kg/24 hr p.o.), anti-asialoGM-1 serum (1 mg/48 hr i.v.) and N omega-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/24 hr i.v.) were given. Graft-infiltrating cells, deposition of cytokines (interferon-gamma [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]), IgM and C, and expression of endothelial cell (EC) P- and E-selectins were investigated by immunohistochemistry. In some cases, rat rTNF-alpha or anti-TNF-alpha antibodies were injected intravenously. Xgs rejected after 3 days by LF-treated rats showed an absence of IgM, C, and T cells, but the infiltration of NK cells and Mphi, together with the presence of IFN...Continue Reading

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