Expression of the c-kit proto-oncogene in rat hepatic allografts during acute rejection.

Abstract

The role of the c-kit proto-oncogene in organ allograft rejection is not known. We investigated the level of c-kit expression following allogeneic transplantation of ACI rat liver grafts into LEW recipients. We studied c-kit mRNA and protein expression in groups of transplant recipients receiving hepatic isografts, hepatic allografts, or hepatic allografts after donor-specific blood transfusion (DST). Pretransplantation DST significantly prolonged survival of hepatic allografts. Infiltrates expressing c-kit were observed in allografts to untreated rats but not in groups receiving isografts or allografts following DST. Northern analysis also demonstrated abundant c-kit mRNA transcripts in the untreated allograft group in contrast to the isograft and the DST-treated groups. In addition, significantly more transcripts for interleukin-12 (IL-12), which is synergistic with c-kit, were present in untreated than in DST-treated allograft groups. In contrast, transforming growth factor beta (TGF-beta), which inhibits c-kit synthesis, was expressed abundantly in hepatic allografts to DST-treated rats but not in allografts to untreated animals. Transcripts for IL-10, which inhibits IL-12 production, were significantly more plentiful in hepatic allografts following DST than in those without DST. The results suggest that c-kit proto-oncogene expression in infiltrating cells is associated with rat hepatic allograft rejection.