Prospective highlights of serum glycoproteins in spontaneous tolerance after orthotopic liver transplantation

Background: We examined the effects and the mechanisms of serum glycoproteins on spontaneous tolerance after orthotopic liver transplantation (OLT) between DA (RT-1^a) and PVG (RT-1^c) rats. Methods: A functional proteome analysis was introduced to investigate differently expressed proteins involved in overcoming major histocompatibility complex (MHC) barriers and lectin blotting was applied to survey the levels of fucosylated proteins. Results: Two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry revealed statistically significant changes in the intensity of 19 proteins at 14 and 60 post-OLT days which respectively corresponded to rejection and tolerance. An interaction network analysis of the identified proteins indicated that the interleukin (IL)-6 signaling pathway might be correlated with the immune events in this model. The peak of IL-6 expression occurred during the recovery period might play a role in the remarkable shifts in the immune response towards spontaneous tolerance. Furthermore, increased levels of IL-6-modulated fucosylation of Igh-6 were also observed during the rejection response while fucosylated hemopexin and haptoglobin were obviously upregulated in the tolerogenic period. Conclusions: These findings suggest that IL-6 and glycoproteins may play critical roles in this spontaneous tolerogenic DA/PVG OLT model and shed light on prolonging hepatic allograft survival in the future.