Expression of Fas and Fas Ligand in Renal Grafts with Acute and Chronic Rejection in the Rat Model

Abstract

The Fas system-based rejection mechanism has not been studied well in terms of cytotoxic T cell activity in graft rejection. We investigated the Fas and Fas ligand level in renal grafts with acute and chronic rejection in a rat model using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Fas ligand in renal allografts was detected as early as 1 day after transplantation in an acute rejection model. It was highly expressed at day 4 and began to decline at day 6 after transplantation. In contrast, Fas ligand in normal kidneys was almost undetectable. Fas ligand in isografts was increased, but the expression level was much lower than in allografts. Interestingly, when Fas ligand expression began to decline in renal allografts, it increased in the spleens of recipients. Fas ligand expression in chronically rejecting allografts was slightly increased, but it was stronger than in isografts. In contrast to Fas ligand gene expression, Fas was constitutively expressed in isografts, allografts, and normal kidneys. However, the Fas level in renal allografts was higher than in normal kidneys. Our data demonstrated that the Fas system might play an important role in acute and chronic rejection by causing apoptosis, and the spleen may eliminate the lymphocytes strongly expressing Fas ligand after completion of the acute rejection.

Analysis of the Fas System and Bcl-2 in Rat Liver Allograft Rejection

“…On day 9, we observed a massive necrosis of hepatocytes and the decreased number of apoptotic cells, suggesting irreversible hepatic failure progressed probably after the peak of acute rejection. These results are similar to previous reports on acute kidney allograft rejection [28], which showed an increased expression of Fas ligand preceding the peak of injury. They demonstrated that the expression of Fas ligand depended on the number of infiltrating leukocytes, which decreased in the late phase of acute rejection.…”

Hyperexpression of the granzyme B inhibitor PI-9 in human renal allografts: A potential mechanism for stable renal function in patients with subclinical rejection

“…During acute rejection, both an increase and a decrease in expression of CD95 in human renal tubular epithelial cells have been described [26][27][28]. The role and engagement of CD95-CD95 ligand pathway inhibitor FLIP during acute rejection in renal transplant recipients is not clarified yet.…”

The Fas and Fas ligand pathways in liver allograft tolerance

“…Total RNA was extracted using a Tri Reagent isolation kit (Molecular Research Center, Inc., Cincinnati, OH), according to the manufacturer's instructions, and dissolved in diethylpyrocarbonatetreated water and quantified by spectrophotometer. Reverse transcription of RNA from sample tissues, followed by polymerase chain reaction (PCR), was used to detect Fas and FasL gene expression [18]. cDNA was synthesized from total RNA in approximately 100 ng in 20 ml of reaction mixture using a first strand cDNA kit (Boehringer Mannheim, Mannheim, Germany), including 1× PCR buffer, 5 mM MgCl 2 , 1 mM dNTP, 50 U RNase inhibitor, 20 U AMV reverse transcriptase, and 1·6 mg oligo(dT) 15 as a primer.…”

“…Alternatively, CD8 þ T cells activated by donor class I antigen may be trapped in the liver and eliminated by receiving a signal to undergo apoptosis in the transplanted liver graft [14,15]. There is recent experimental evidence that manipulation of the Fas/Fas ligand (FasL) system might provide this type of apoptosis signal to induce allospecific immunosuppression [16][17][18].…”