Over-expression of AIF-1 in liver allografts and peripheral blood correlates with acute rejection after transplantation in rats

Am J Transplant. 2004 Dec;4(12):1949-57. doi: 10.1111/j.1600-6143.2004.00621.x.


Early and accurate detection of acute cellular rejection (ACR) is important in the management of liver allograft recipients. We hypothesized that expression of allograft inflammatory factor (AIF)-1 would be associated with liver allograft rejection as previous studies have shown that a relationship exists between kidney and heart transplantation. Indeed using rat orthotopic transplant models we found that the expression of allograft inflammatory factor-1 (AIF-1) can be detected in both allograft and peripheral blood leukocytes with peak levels detected 7 days following liver transplantation. Interestingly, AIF-1 expression increased 2-fold in acutely rejecting liver allografts compared to chronically accepted livers on days 5, 7 and 10 after transplantation. AIF-1 expression in peripheral blood leukocytes was also significantly greater in the rejection model than in the acceptance model. Flow cytometric analysis of peripheral blood leukocytes demonstrated that AIF-1 was expressed in ED2-positive cells, a marker for Kupffer cells. In vitro studies showed that AIF-1 expression in Kupffer cells was up-regulated by coculture with Th1 cytokines. However, neither LPS nor Escherichia coli (E. coli) administration had an affect on AIF-1 expression. These data indicate that high levels of AIF-1 expression reflect aggressive liver allograft rejection and suggest a role for monitoring AIF-1 in peripheral blood leukocytes as a monitor for increased immunosuppression.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Calcium-Binding Proteins / blood*
  • Calcium-Binding Proteins / genetics
  • Disease Models, Animal
  • Gene Expression Regulation
  • Graft Rejection / blood*
  • Graft Rejection / pathology
  • Liver Transplantation / pathology*
  • Male
  • Microfilament Proteins
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred Lew
  • Transcription, Genetic
  • Transplantation, Homologous
  • Transplantation, Isogeneic


  • Aif1 protein, rat
  • Biomarkers
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • RNA, Messenger