Gadolinium chloride suppresses acute rejection and induces tolerance following rat liver transplantation by inhibiting Kupffer-cell activation.
The aim of the present study was to investigate the mechanism by which gadolinium chloride (GdCl3) inhibits Kupffer cell (KC) activation and its ability to suppress acute rejection and induce tolerance following liver transplantation in rats. Rats were randomly divided into control, liver transplantation with GdCl3pretreatment and liver transplantation with normal saline pretreatment groups. The survival rate, liver function, hepatic pathological histology, cytokine levels in the liver and bile, activity of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in KCs, and expression levels of membranous molecules on the KCs were observed. It was identified that the one-month survival rate in the GdCl3group was significantly higher compared with that in the saline group (P<0.05). The liver function in the GdCl3group gradually recovered following transplantation surgery; however, it progressively deteriorated in the saline group. There were minor changes of hepatic pathological histology in the GdCl3group, whereas changes typical of acute rejection occurred in the saline group. In the GdCl3group, the levels of interferon γ and interleukin (IL)-2 were significantly lower whereas the levels of IL-10 were significantly higher compared with those in the control and saline groups (all P<0.01). The IL-4 levels in the GdCl3and control groups were similar. The activity of NF-κB in the saline group was significantly higher compared with those in the control and GdCl3groups (P<0.01). The expression levels of major histocompatibility complex-II, cluster of differentiation (CD)80 and CD86 on the KC membranes in the GdCl3group was significantly lower compared with those in the control group (P<0.05); however, these membranous proteins were highly expressed in the saline group. These data indicate that GdCl3efficiently inhibits the immunological activity of KCs, suppresses acute rejection and induces tolerance following liver allograft transplantation in rats.
Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan 629000, P.R. China ; Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Yakun
Y
Wu
Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Yunbing
Y
Wang
Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan 629000, P.R. China ; Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Min
M
Li
Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan 629000, P.R. China ; Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Xiaoli
X
Yang
Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Jianping
J
Gong
Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan 629000, P.R. China.
Wei
W
Zhang
Kupffer cells; gadolinium chloride; liver transplantation