ABSTRACT
The category of chronic antibody-mediated rejection (AMR) is not included in Banff schema for liver allograft rejection. In the present study, we examined the pathology of chronic rejection using rat liver transplantation. Orthotopic liver transplantation from Lewis to BN rats was performed without immunosuppression, and with or without HA reconstruction. We studied grafts at day 120 for arterialized and day 39 for nonarterialized transplants focusing on the immunoglobulin G (IgG) deposition and the pathologic characteristics of rejection. About 20% of arterialized grafts survived more than 120 days. Between day 7 and day 120, T-cell infiltration to arterialized grafts was accompanied by IgG deposition in portal veins, hepatic arteries, and bile ducts in portal areas, sinusoids and hepatocytes. At day 120, arterialized grafts were morphologically characterized by late chronic rejection with IgG deposition, intraluminal portal veins fibrosis, intimal fibrous thickening of hepatic arteries, diffuse sinusoidal fibrosis, as well as injury and loss of bile ducts due to fibrosis. The severities of T cell-mediated rejection and AMR were higher in nonarterialized than arterialized grafts. Nonarterialized Lewis liver grafts in BN rats were rejected by day 39, as characterized by late chronic rejection with IgG deposition and cellular infiltration. In conclusion, chronic AMR may be involved in chronic rejection of liver transplantations. When chronic AMR was involved in chronic liver graft rejection, typical late morphological changes emerged within a short period.
Subject(s)
Antibodies/immunology , Graft Rejection/immunology , Liver Transplantation , Animals , Rats , Rats, Inbred LewABSTRACT
BACKGROUND: Hepatic artery (HA) reconstruction is performed in the clinical liver transplantation. METHODS: We assessed the importance of HA reconstruction in the success of liver transplantation. Orthotopic liver transplantation was performed without immunosspression from Lewis (RT1l) to Lewis rats (syngeneic transplantation) as well as Lewis to BN (RT1n) rats (allogeneic transplantation) with or without HA reconstruction. We examined graft function, pathology, and mRNA levels using DNA arrays in both arterialized and nonarterialized liver grafts. RESULTS: In Lewis-to-Lewis syngeneic grafts, both the arterialized and nonarterialized grafts survived >120 days with normal graft function. lnfiltration of CD3(+) T cells and CD68(+) macrophages, marked bile duct proliferation with apoptotic epithelial cells, and expansion and increasing fibrosis of portal areas were evident in the nonarterialized grafts at day 120, although preservation of architecture was noted in the arterialized grafts. DNA array analysis of nonarterialized syngeneic grafts demonstrated the upregulation of mRNA of cell death-related proteins, cell cycle-related proteins, and inflammation-related proteins than those in arterialized grafts. Moreover, the arterialized Lewis-to-BN allogeneic grafts could survive for a long time with less severe graft dysfunction than those in non-arterialized allogeneic grafts. CONCLUSIONS: HA reconstruction in liver transplantation inhibited hypoxic injury and subsequent inflammation and bile duct proliferation, prevented the augmentation of T-cell-and antibody-mediated rejection, and mediated long-term graft acceptance. HA reconstruction is essential factor in the success of liver transplantation.
Subject(s)
Graft Rejection/prevention & control , Graft Survival , Hepatic Artery/surgery , Ischemia/prevention & control , Liver Transplantation , Liver/blood supply , Animals , Rats , Rats, Inbred LewSubject(s)
Cyclopropanes/pharmacology , Intestine, Large/metabolism , Water , Animals , Biological Transport , Cecum/anatomy & histology , Cecum/metabolism , Female , Male , Methods , Rats , TritiumABSTRACT
Pauling and Miller have independently proposed that the presence of an anesthetic gas in tissue induces a cage-like arrangement of hydrogen-bonded water molecules. The theories recognize that most gas-hydrate crystals would not form at the temperature and pressure that exist during anesthesia and propose that other components of tissue such as protein should have a stabilizing effect. Measurements of the behavior of water, rather than the anesthetic agent, would provide alternative information about the likelihood of hydrate crystal formation and this information could be such as to be applicable to body temperature and to pressures used for anesthesia. If the number of hydrogen-bonded water molecules in tissue is increased, then the movement of an average water molecule should be hindered. Movement of water through the tissue may be measured by tagging it with tritium and the anesthetic gas should then slow the movement of tritiated water through the tissue. The flux of tritiated water through rat cecum is indeed slowed when the cecum is exposed to the anesthetic gas, xenon, which can participate biochemically only by virtue of its van der Waals interaction. The decrement in water flux is in reasonable agreement with what could be expected theoretically from calculations based on the activation energy for the self-diffusion of water and the degree of hypothermia necessary to produce narcosis.