Submitted on November 27, 2007
Accepted on February 20, 2008
Activation of innate immunity (NK/IFN-
) in rat allogeneic liver transplantation: Contribution to liver injury and suppression of hepatocyte proliferation
Kezhen Shen1, Shu-sen Zheng2, Ogyi Park1, Hua Wang3, Zhaoli Sun4, and Bin Gao1*
1 Section on Liver Biology, NIAAA, Bethesda, Maryland, United States
2 Zhejing University School of Medicine, China
3 NIAAA, Section on Liver Biology, United States
4 Johns Hopkins, Balitmore, Maryland, United States
* To whom correspondence should be addressed. E-mail: bgao{at}mail.nih.gov.
Liver transplantation is currently the only treatment for patients with end-stage liver disease. However, the mechanisms underlying liver injury and hepatocyte proliferation post transplantation remain obscure. In this investigation, we compared liver injury and hepatocyte proliferation in syngeneic and allogeneic animal models. Male Lewis and Dark Agouti (DA) rats were subjected to orthotopic liver transplantation (OLT). Rat OLT was performed in syngeneic (Lewis-Lewis) and allogeneic (Lewis-DA, DA-Lewis) animal models. Allogeneic liver grafts exhibited greater injury and cellular apoptosis than syngeneic grafts, but showed less hepatocyte proliferation after OLT. Additionally, expression of IFN-
mRNA and activation of the downstream signal (STAT1) and genes (IRF-1 and p21) were greater in the allogeneic grafts compared with the syngeneic grafts. In contrast, activation of STAT3 decreased in allogeneic grafts. Depletion of NK cells decreased IFN-/STAT1 activation, but enhanced hepatocyte proliferation in the allogeneic grafts. These findings suggest that compared with the syngeneic grafts, innate immunity (NK/IFN-) is activated post allogeneic transplantation, which likely attributes to liver injury and inhibits hepatocyte proliferation.
