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

Yuichi Nagakawa, Shuji Nomoto, Yukihiko Kato, Robert A. Montgomery, George Melville Williams, Andrew S. Klein, Zhaoli Sun

Research output: Contribution to journalArticlepeer-review

Abstract

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 co-culture 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.

Original languageEnglish (US)
Pages (from-to)1949-1957
Number of pages9
JournalAmerican Journal of Transplantation
Volume4
Issue number12
DOIs
StatePublished - Dec 2004

Keywords

  • AIF-1
  • Acute rejection
  • Blood
  • Kupffer cells
  • Liver transplantation
  • Rat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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