title: Over-expression of AIF-1 in liver allografts and peripheral blood correlates with acute rejection after transplantation in rats.
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 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.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nagakawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: George Melville
authors.initials: GM
authors.lastname: Williams
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Klein
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000097:blood* / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: C100745:Aif1 protein, rat; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger