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 Avery Montgomery, George M 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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